Affinage

SSTR2

Somatostatin receptor type 2 · UniProt P30874

Length
369 aa
Mass
41.3 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SSTR2 is a Gi/Go-coupled somatostatin receptor that integrates inhibitory control over secretion, proliferation, and inflammation across endocrine, gastrointestinal, and neuroendocrine tissues. Ligand binding—dependent on Asp122 in TM3 for a direct ionic contact with somatostatin Lys9 and on Phe/Asn residues in TM6/7 for octreotide selectivity—activates pertussis toxin-sensitive Gi (preferentially Giα3 and Goα2) to inhibit adenylyl cyclase, suppress voltage-gated Ca²⁺ currents, and open GIRK channels, thereby hyperpolarizing secretory cells and inhibiting exocytosis in pancreatic islets, pituitary, and cholangiocytes (PMID:8098703, PMID:22932785, PMID:12676656, PMID:7882976, PMID:7488212). SSTR2 also stimulates tyrosine phosphatase activity to mediate antiproliferative signaling—including cell-cycle arrest and apoptosis—and can activate phospholipase C and Ca²⁺ mobilization through partially PTX-insensitive routes requiring transmembrane-domain determinants beyond the intracellular loops (PMID:7907795, PMID:7910018, PMID:9228036, PMID:19148511). Agonist-induced internalization proceeds via clathrin-coated pits and is regulated by transient interactions with filamin A along actin fibers, while SSTR2 surface expression is itself modulated by miR-375 (PMID:29931263, PMID:40488558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1993 High

    Establishing the primary signaling output: SSTR2 was shown to inhibit adenylyl cyclase through pertussis toxin-sensitive Gi proteins, with preferential coupling to Giα3 and Goα2, resolving why SSTR2 failed to inhibit cAMP in certain cellular backgrounds lacking the appropriate Gα subunit.

    Evidence Immunoprecipitation with subtype-specific G-protein antisera in CHO and HEK293 cells; cAMP accumulation assays in CHO cells stably expressing rat SSTR2

    PMID:8096694 PMID:8098703

    Open questions at the time
    • Whether Giα1 or Giα3 is the physiologically dominant partner remained unresolved across studies (cf. PMID:7914078 reporting Giα1 coupling)
    • Endogenous stoichiometry of Gα subunits in native tissues not addressed
  2. 1994 High

    Defining dual signaling: beyond cAMP inhibition, SSTR2 was found to stimulate PLC/Ca²⁺ mobilization through a partially PTX-insensitive mechanism and to suppress voltage-gated Ca²⁺ currents, establishing it as a multi-effector GPCR.

    Evidence cAMP, inositol phosphate, and Ca²⁺ assays with PTX in COS-7 cells; whole-cell patch clamp in RINm5F insulinoma cells expressing SSTR2

    PMID:7910018 PMID:7982482 PMID:8144617

    Open questions at the time
    • Identity of the PTX-insensitive G protein mediating PLC activation not determined
    • Whether Ca²⁺ current inhibition and PLC activation occur in the same native cell type
  3. 1994 High

    Mapping the ligand-binding pocket: two residues in TM6 (Gln291→Asn) and TM7 (Ser305→Phe) were identified as primary determinants of octreotide selectivity, providing a structural rationale for SSTR2's pharmacological profile.

    Evidence Systematic site-directed mutagenesis swapping SSTR1 residues to SSTR2 identities; radioligand binding quantification

    PMID:7882976

    Open questions at the time
    • No crystal or cryo-EM structure available at the time to validate modeled contacts
    • Contributions of extracellular loops not systematically tested
  4. 1995 High

    Identifying the antiproliferative effector: SSTR2-mediated growth inhibition was linked to stimulation of tyrosine phosphatase activity (blocked by orthovanadate), mechanistically distinguishing it from SSTR5's Ca²⁺-dependent antiproliferative pathway, and a direct Asp122–Lys9 ionic contact was established by reciprocal charge-switch mutagenesis.

    Evidence Tyrosine phosphatase and proliferation assays across five SSTR subtypes in CHO cells; charge-switch mutagenesis of rat SSTR2 Asp122 with complementary somatostatin analogues

    PMID:7488212 PMID:7878022

    Open questions at the time
    • The specific tyrosine phosphatase(s) activated by SSTR2 not identified
    • Structural basis of Asp122–Lys9 interaction not confirmed by biophysical methods
  5. 1997 High

    Resolving the structural basis of PLC coupling: chimeric receptors showed that SSTR2's intracellular loops alone are insufficient for PLC activation—transmembrane domain sequences are additionally required—while being sufficient for cAMP inhibition.

    Evidence SSTR1/SSTR2 chimeric receptors expressed in pituitary GH12C1 and F4C1 cells; cAMP, PLC, and Ca²⁺ assays

    PMID:9228036

    Open questions at the time
    • Specific transmembrane residues required for PLC coupling not mapped
    • Role of receptor oligomerization in PLC coupling not addressed
  6. 2002 High

    Defining physiological sites of action: SSTR2 was localized to gastric parietal cells, ECL cells, and NOS-positive myenteric neurons using a genetic knockin reporter, and shown to regulate bile duct secretion and absorption through cAMP inhibition and cGMP elevation, with complete loss of function in SSTR2 knockout mice.

    Evidence Sstr2-lacZ knockin mice with cell-type immunostaining; SSTR2 KO vs. WT bile duct units with selective agonist and second-messenger assays

    PMID:12442323 PMID:12676656

    Open questions at the time
    • Mechanism of SSTR2-mediated cGMP increase not defined
    • Relative contribution of SSTR2 versus other SSTRs in GI physiology in vivo not quantified
  7. 2012 High

    Establishing the secretory inhibition mechanism in human islets: SSTR2 was shown to be the dominant receptor subtype inhibiting insulin and glucagon secretion by activating GIRK channels, suppressing P/Q-type Ca²⁺ currents, and directly inhibiting exocytosis downstream of Ca²⁺.

    Evidence Patch clamp electrophysiology and capacitance measurements in primary human islet cells with SSTR2-selective agonists

    PMID:22932785

    Open questions at the time
    • Molecular identity of the exocytotic target inhibited downstream of Ca²⁺ not identified
    • Whether SSTR2/SSTR3 heterodimerization (shown in HEK293 cells, PMID:22651821) occurs in native islets
  8. 2018 High

    Elucidating the internalization mechanism: single-molecule imaging revealed that filamin A transiently interacts with SSTR2 along actin fibers to restrain diffusion, promote clustering, and facilitate recruitment to clathrin-coated pits for agonist-induced endocytosis.

    Evidence Fast multicolor single-molecule microscopy with dominant-negative FLNA fragment in live cells

    PMID:29931263

    Open questions at the time
    • FLNA binding site on SSTR2 not mapped
    • Whether β-arrestin and FLNA act sequentially or cooperatively in internalization not resolved
  9. 2024 Medium

    Extending SSTR2 signaling to inflammasome regulation: cortistatin/SSTR2 signaling was shown to activate AMPK, inhibit Drp1-mediated mitochondrial fission, reduce ROS, and suppress NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes during sepsis.

    Evidence SSTR2 pharmacological inhibition and genetic knockout in a mouse sepsis model; Western blotting for AMPK/Drp1/NLRP3/gasdermin D pathway

    PMID:38733824

    Open questions at the time
    • Mechanism linking SSTR2/Gi to AMPK activation not defined
    • Not independently replicated
    • Relevance of this pathway outside sepsis models unknown
  10. 2025 Medium

    Identifying epigenetic regulation of receptor availability: miR-375 was shown to downregulate SSTR2 expression in corticotroph pituitary cells, with functional consequences for octreotide-induced internalization and apoptosis, linking glucocorticoid signaling to SSTR2 surface density.

    Evidence miR-375 inhibitor transfection in AtT20 cells and human primary corticotroph cultures; Western blot, immunofluorescence, apoptosis assays

    PMID:40488558

    Open questions at the time
    • Whether miR-375 directly targets the SSTR2 3′-UTR or acts indirectly not confirmed by luciferase reporter assay
    • In vivo relevance in pituitary tumors not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the specific tyrosine phosphatase(s) mediating SSTR2 antiproliferative signaling, the structural basis of dual G-protein coupling including the PTX-insensitive PLC pathway, the FLNA-binding determinants on SSTR2, and the physiological relevance of SSTR2/SSTR3 heterodimerization in native tissues.
  • No high-resolution structure of SSTR2 in complex with Gi or with filamin A
  • Tyrosine phosphatase identity downstream of SSTR2 remains unknown
  • Physiological significance of SSTR2/SSTR3 heterodimerization unconfirmed in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 1
Partners
FLNAGNAI1GNAI3GNAO1SSTR3

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 SSTR2 selectively associates with Gi alpha 3 and G(o) alpha 2 proteins, as demonstrated by immunoprecipitation with peptide-directed antisera; SSTR2's inability to efficiently associate with Gi alpha 1 explains its failure to mediate cAMP inhibition in HEK 293 cells. Immunoprecipitation with subtype-specific antisera against G-protein alpha subunits in CHO and HEK 293 cells The Journal of biological chemistry High 8098703
1993 Rat SSTR2 expressed in CHO cells is coupled to inhibition of forskolin-stimulated cAMP accumulation (EC50 ~350 pM for somatostatin-14), establishing its primary signaling pathway. Stable transfection of CHO cells with rat SSTR2 cDNA; radioligand binding and cAMP accumulation assays Biochemical and biophysical research communications High 8096694
1994 SSTR2 stimulates tyrosine phosphatase activity and inhibits cell proliferation; both effects occur at similar potencies, implicating tyrosine phosphatase as a transducer of the SSTR2-mediated growth inhibition signal. Transfection of COS-7 and NIH 3T3 cells with human SSTR1 or SSTR2; radioligand binding, tyrosine phosphatase activity assays, and cell proliferation assays with somatostatin analogues RC-160 and SMS 201-995 Proceedings of the National Academy of Sciences of the United States of America High 7907795
1994 SSTR2 couples to both inhibition of adenylyl cyclase (pertussis toxin-sensitive) and stimulation of phospholipase C / Ca2+ mobilization (partially PTX-insensitive), demonstrating dual G-protein signaling. Transfection of COS-7 cells with human SSTR2 cDNA; cAMP accumulation, inositol phosphate, and intracellular Ca2+ assays with pertussis toxin pretreatment Biochemical and biophysical research communications High 7910018
1994 SSTR2 couples exclusively to pertussis toxin-sensitive G proteins for ligand binding regulation, whereas SSTR1 couples to both pertussis-sensitive and -insensitive G proteins; only SSTR1 (not SSTR2) mediates somatostatin inhibition of Na+/H+ exchange, and this requires sequences spanning the second through sixth hydrophobic domains including both second and third cytoplasmic loops. Stable expression in mouse Ltk- and HEK293 cells; GTPγS and pertussis toxin binding experiments; Na+/H+ exchange assays; chimeric receptor construction The Journal of biological chemistry High 8144617
1994 Human SSTR2 is functionally coupled to Gi alpha 1 protein for adenylyl cyclase inhibition; somatostatin inhibits cAMP formation only when SSTR2 is co-expressed with Gi alpha 1, not with Gi alpha 2 or Gi alpha 3, in CHO cells. Stable co-expression of human SSTR2 with individual Gi alpha subunit cDNAs in CHO cells; pertussis toxin-sensitive cAMP accumulation assay Biochemical and biophysical research communications High 7914078
1994 Two amino acids in transmembrane domains VI (Gln291→Asn) and VII (Ser305→Phe) of SSTR2 are the primary determinants of high-affinity, selective binding of SMS 201-995 (octreotide); single Ser305Phe mutation increased SSTR1 affinity for SMS 201-995 ~100-fold. Site-directed mutagenesis of SSTR1 with sequential introduction of SSTR2 residues; radioligand binding in transfected cells; molecular modeling based on bacteriorhodopsin structure The EMBO journal High 7882976
1994 SSTR1 and SSTR2 both mediate inhibition of adenylyl cyclase via pertussis toxin-sensitive G-proteins when expressed in CHO cells, recognizing SS-14 and SS-28 with high affinity and MK678 selectively identifying SSTR2. Stable expression of rat SSTR1 and SSTR2 in CHO-K1 cells; radioligand binding; adenylyl cyclase inhibition assays with pertussis toxin Endocrinology High 7907016
1994 SSTR2 mediates inhibition of high-voltage-activated Ca2+ currents in response to somatostatin and SMS 201-995 in RINm5F insulinoma cells, whereas SSTR1-expressing cells show no Ca2+ current inhibition. Stable expression of human SSTR1 or SSTR2 in RINm5F cells; whole-cell patch clamp electrophysiology FEBS letters High 7982482
1995 SSTR2-mediated growth inhibition operates through tyrosine phosphatase stimulation (blocked by orthovanadate), while SSTR5 inhibits growth through suppression of CCK-stimulated intracellular calcium mobilization, demonstrating mechanistically distinct anti-proliferative pathways for each receptor subtype. CHO cells stably expressing individual SSTR subtypes; tyrosine phosphatase assays, intracellular Ca2+ measurements, cell proliferation assays with pharmacological inhibitors Proceedings of the National Academy of Sciences of the United States of America High 7878022
1995 A critical aspartate residue (Asp122) in transmembrane domain 3 of rat SSTR2 interacts with Lys9 of somatostatin-14; charge-switch mutants D122K and Asp9-somatostatin-14 reciprocally rescue binding affinity, identifying a direct contact site. Site-directed mutagenesis (D89A, D89E, D122K) of rat SSTR2; radioligand binding assays with mutant somatostatin analogues Biochemical and biophysical research communications High 7488212
1995 SSTR2 mediates phospholipase C-independent Ca2+ mobilization by opening cell-surface calcium channels (not intracellular stores), as Ca2+ increase was abolished by calcium-free medium and not accompanied by inositol phosphate turnover in AR42J cells. Pharmacological characterization with subtype-selective agonists in rat AR42J pancreatic cells; intracellular Ca2+ measurements in calcium-free medium; inositol phosphate assay Biochemical and biophysical research communications Medium 7669056
1996 SSTR2 couples to inhibition of an L-type Ca2+ current via pertussis toxin-sensitive G proteins in AtT-20 pituitary cells; this coupling is not desensitized by agonist pretreatment, distinguishing it from SSTR5 coupling to the same channel. Whole-cell patch clamp in AtT-20 cells with SSTR2- and SSTR5-selective agonists and pertussis toxin pretreatment Neuroscience High 8684611
1997 SSTR2 couples to PLC activation in pituitary cells via a mechanism requiring sequences beyond the intracellular loops; chimeric receptors containing only intracellular loops of SSTR2 in an SSTR1 backbone mediate cAMP inhibition but fail to activate PLC, indicating transmembrane domain contributions. Expression of SSTR1, SSTR2, and chimeric receptors in rat pituitary GH12C1 and F4C1 cells; cAMP, PLC, Ca2+ assays; pertussis toxin treatment The Journal of biological chemistry High 9228036
2002 SSTR2 is expressed on parietal cells and enterochromaffin-like (ECL) cells in the stomach, and on NOS-positive neurons in the myenteric plexus of the gastrointestinal tract, as identified by lacZ knockin reporter mice combined with cell-type-specific antibody co-labeling. Sstr2 knockin/lacZ mouse model; beta-galactosidase staining combined with immunostaining for H+K+ATPase, histidine decarboxylase, SSTR2a, and NOS The Journal of comparative neurology High 12442323
2003 Somatostatin regulates ductal bile formation via SSTR2 on cholangiocytes by both inhibiting secretin-stimulated ductal fluid secretion and stimulating ductal fluid absorption; these effects involve intracellular cGMP increase and cAMP inhibition and are completely absent in SSTR2 knockout mice. Isolated intrahepatic bile duct units (IBDUs) from wild-type and SSTR2 knockout mice; selective SSTR2 agonist L-779976; fluid movement, cAMP, and cGMP measurements American journal of physiology. Cell physiology High 12676656
2012 In human pancreatic beta- and alpha-cells, SST inhibits secretion predominantly through SSTR2 by activating GIRK channels causing membrane hyperpolarization, suppressing P/Q-type Ca2+ currents, and directly inhibiting exocytosis downstream of Ca2+ entry. Patch clamp electrophysiology, exocytosis measurements, and subtype-selective agonists in human islet cells; SSTR2-selective agonist vs. SSTR5 agonist comparison American journal of physiology. Endocrinology and metabolism High 22932785
2018 FLNA (filamin A) undergoes transient interactions with SSTR2 preferentially along actin fibers; these interactions restrain SSTR2 diffusion, promote SSTR2 clustering and recruitment to clathrin-coated pits (CCPs), and are required for agonist-induced SSTR2 internalization. A dominant-negative FLNA fragment increases SSTR2 mobility and impairs internalization. Fast multicolor single-molecule microscopy (live cell imaging) of individual SSTR2 and FLNA molecules; dominant-negative FLNA fragment; quantification of CCP recruitment Endocrinology High 29931263
2002 SSTR2 mediates somatostatin-induced increase in intracellular Ca2+ and insulin secretion in HIT-T15 beta cells in the presence of arginine vasopressin; the SSTR2-selective agonist L-779,976 recapitulates these effects, and a specific SSTR2 antagonist (PRL-2903) abolishes them. Subtype-selective agonists (for SSTR1-5) and SSTR2 antagonist in HIT-T15 cells; intracellular Ca2+ measurements and insulin secretion assays Life sciences Medium 12084389
2024 Cortistatin specifically binds SSTR2 and activates AMPK, which inhibits Drp1-mediated mitochondrial fission, reduces ROS, and suppresses NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes during sepsis; pharmacological inhibition and genetic ablation of SSTR2 both abolish these effects. SSTR2 pharmacological inhibition and genetic knockout in mouse sepsis model; AMPK/Drp1/NLRP3 pathway western blotting; caspase-1, IL-1β, gasdermin D cleavage assays International immunopharmacology Medium 38733824
2006 SSTR2 overexpression in pancreatic cancer cells inhibits migration and invasion by reducing MMP-2 expression and increasing TIMP-2 expression. Adenovirus-mediated SSTR2 transfection into BXPC-3 pancreatic cancer cells; Matrigel Transwell invasion assay; RT-PCR for MMP-2 and TIMP-2 Journal of Huazhong University of Science and Technology. Medical sciences Medium 16711011
2009 SSTR2 inhibits cancer cell proliferation via both cytostatic (cell cycle arrest) and cytotoxic (apoptosis) pathways; SSTR2 overexpression increases these effects in both SSTR2-positive and SSTR2-negative cancer cell lines, and the anti-proliferative effect is blocked by orthovanadate. Adenoviral SSTR2 overexpression in capan-2 and A549 cancer cells; cell cycle analysis; apoptosis immunoassays; xenograft growth assays Oncology reports Medium 19148511
2012 SSTR2/SSTR3 heterodimerize at the plasma membrane; agonist stimulation promotes receptor internalization with increased intracellular colocalization; co-expression modulates ERK1/2 and p38 MAPK signaling and causes Gi-dependent inhibition of cell proliferation with increased PARP-1 and TUNEL staining. Co-transfection of SSTR2 and SSTR3 in HEK-293 cells; confocal colocalization; co-immunoprecipitation; cAMP, ERK1/2, p38 phosphorylation, and apoptosis assays Journal of molecular signaling Medium 22651821
2017 SSTR2 activation by octreotide prevents high glucose-induced occludin downregulation in RF/6A cells via inhibition of VEGF secretion and suppression of NRP1/Akt/ERK signaling; SSTR2 antagonist reverses octreotide's protective effect. RF/6A cells treated with octreotide ± SSTR2 antagonist (c-SOM) and NRP1 inhibitor; Western blot for occludin, VEGF, p-Akt, p-ERK; ELISA for VEGF Experimental and therapeutic medicine Low 28810643
2025 miR-375 epigenetically downregulates SSTR2 expression in corticotroph pituitary cells; dexamethasone increases miR-375 levels, reducing SSTR2 membrane expression; miR-375 inhibition increases SSTR2 membrane protein expression, enhances octreotide-induced internalization, and potentiates octreotide-induced apoptosis via PARP, Caspase-3, and ERK1/2 phosphorylation. miR-375 inhibitor transfection in AtT20 cells and human primary corticotroph cultures; Western blot, immunofluorescence, RT-qPCR for SSTR2; proliferation and flow cytometry apoptosis assays Endocrinology Medium 40488558

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proceedings of the National Academy of Sciences of the United States of America 322 7907795
1994 Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Cancer research 294 8012966
1995 Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proceedings of the National Academy of Sciences of the United States of America 279 7878022
1997 Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. The Journal of clinical investigation 266 9045884
1993 Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. Biochemical and biophysical research communications 152 8386508
1993 Gi alpha 3 and G(o) alpha selectively associate with the cloned somatostatin receptor subtype SSTR2. The Journal of biological chemistry 144 8098703
2012 SSTR2 is the functionally dominant somatostatin receptor in human pancreatic β- and α-cells. American journal of physiology. Endocrinology and metabolism 129 22932785
1994 Localization of somatostatin (SRIF) SSTR-1, SSTR-2 and SSTR-3 receptor mRNA in rat brain by in situ hybridization. Naunyn-Schmiedeberg's archives of pharmacology 108 8170498
1995 Two amino acids, located in transmembrane domains VI and VII, determine the selectivity of the peptide agonist SMS 201-995 for the SSTR2 somatostatin receptor. The EMBO journal 105 7882976
1994 Differential expression of messenger RNAs for somatostatin receptor subtypes SSTR1, SSTR2 and SSTR3 in adult rat brain: analysis by RNA blotting and in situ hybridization histochemistry. Neuroscience 103 8190266
1994 Detection of somatostatin receptor subtype 2 (SSTR2) in established tumors and tumor cell lines: evidence for SSTR2 heterogeneity. Peptides 100 7854974
1996 Somatostatin receptor subtypes SSTR2 and SSTR5 couple negatively to an L-type Ca2+ current in the pituitary cell line AtT-20. Neuroscience 73 8684611
1994 Subtype-specific signaling mechanisms of somatostatin receptors SSTR1 and SSTR2. The Journal of biological chemistry 67 8144617
2004 Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: molecular imaging after systemic delivery using 111In-pentetreotide. Molecular therapy : the journal of the American Society of Gene Therapy 65 15336655
2006 Quantitative assessment of SSTR2 expression in patients with non-small cell lung cancer using(68)Ga-DOTATOC PET and comparison with (18)F-FDG PET. European journal of nuclear medicine and molecular imaging 63 16570185
1995 Patterns of expression of SSTR1 and SSTR2 somatostatin receptor subtypes in the hypothalamus of the adult rat: relationship to neuroendocrine function. Neuroscience 63 7777168
1995 Morphine cross-reacts with somatostatin receptor SSTR2 in the T47D human breast cancer cell line and decreases cell growth. Cancer research 61 7585646
1994 Transfected human somatostatin receptor type 2, SSTR2, not only inhibits adenylate cyclase but also stimulates phospholipase C and Ca2+ mobilization. Biochemical and biophysical research communications 57 7910018
2013 Ki-67 is a predictor of acromegaly control with octreotide LAR independent of SSTR2 status and relates to cytokeratin pattern. European journal of endocrinology 56 23749849
1994 T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA. Journal of immunology (Baltimore, Md. : 1950) 54 7913111
2017 Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors. International journal of cancer 51 28120505
1993 The rat SSTR2 somatostatin receptor subtype is coupled to inhibition of cyclic AMP accumulation. Biochemical and biophysical research communications 50 8096694
2002 Identification of cells expressing somatostatin receptor 2 in the gastrointestinal tract of Sstr2 knockout/lacZ knockin mice. The Journal of comparative neurology 48 12442323
2003 Somatostatin stimulates ductal bile absorption and inhibits ductal bile secretion in mice via SSTR2 on cholangiocytes. American journal of physiology. Cell physiology 47 12676656
1995 Characterization and distribution of somatostatin SS-1 and SRIF-1 binding sites in rat brain: identity with SSTR-2 receptors. European journal of pharmacology 47 7781707
1994 Somatostatin receptor subtype SSTR2 mediates the inhibition of high-voltage-activated calcium channels by somatostatin and its analogue SMS 201-995. FEBS letters 47 7982482
1994 The somatostatin receptors SSTR1 and SSTR2 are coupled to inhibition of adenylyl cyclase in Chinese hamster ovary cells via pertussis toxin-sensitive pathways. Endocrinology 46 7907016
2019 Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo. Journal of medicinal chemistry 42 30735385
2017 DNA methylation of CMTM3, SSTR2, and MDFI genes in colorectal cancer. Gene 42 28782576
1995 Identification of a critical aspartate residue in transmembrane domain three necessary for the binding of somatostatin to the somatostatin receptor SSTR2. Biochemical and biophysical research communications 42 7488212
2024 Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma. Clinical cancer research : an official journal of the American Association for Cancer Research 41 38048045
2001 Somatostatin receptor (SSTR) expression and function in normal and leukaemic T-cells. Evidence for selective effects on adhesion to extracellular matrix components via SSTR2 and/or 3. Clinical and experimental immunology 40 11472428
1996 Expression of somatostatin receptor (SSTR) subtypes in pituitary adenomas: quantitative analysis of SSTR2 mRNA by reverse transcription-polymerase chain reaction. Journal of neuroendocrinology 38 8866248
1997 Both overlapping and distinct signaling pathways for somatostatin receptor subtypes SSTR1 and SSTR2 in pituitary cells. The Journal of biological chemistry 35 9228036
2020 Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy. Cancer gene therapy 34 32684623
2017 Anti-SSTR2 peptide based targeted delivery of potent PLGA encapsulated 3,3'-diindolylmethane nanoparticles through blood brain barrier prevents glioma progression. Oncotarget 33 29029435
2013 Inhibition of tumor promoting signals by activation of SSTR2 and opioid receptors in human breast cancer cells. Cancer cell international 33 24059654
2021 SSTR2 Expression in Olfactory Neuroblastoma: Clinical and Therapeutic Implications. Head and neck pathology 32 33929681
2019 Prevalence and Clinical Correlations of Somatostatin Receptor-2 (SSTR2) Expression in Neuroblastoma. Journal of pediatric hematology/oncology 31 30334904
2009 Somatostatin analogues inhibit cancer cell proliferation in an SSTR2-dependent manner via both cytostatic and cytotoxic pathways. Oncology reports 26 19148511
2023 Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response. Molecular pharmaceutics 25 37788300
2022 Heterogeneity of SSTR2 Expression Assessed by 68Ga-DOTATOC PET/CT Using Coefficient of Variation in Patients with Neuroendocrine Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 24 35273092
2007 Nuclear uptake and dosimetry of 64Cu-labeled chelator somatostatin conjugates in an SSTr2-transfected human tumor cell line. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 24 17631550
2018 Single-Molecule Microscopy Reveals Dynamic FLNA Interactions Governing SSTR2 Clustering and Internalization. Endocrinology 23 29931263
2013 ZAC1 and SSTR2 are downregulated in non-functioning pituitary adenomas but not in somatotropinomas. PloS one 23 24098585
2009 Overexpression of SSTR2 inhibited the growth of SSTR2-positive tumors via multiple signaling pathways. Acta oncologica (Stockholm, Sweden) 22 18759148
1995 Somatostatin (SSTR2) receptors mediate phospholipase C-independent Ca2+ mobilization in rat AR42J pancreas cells. Biochemical and biophysical research communications 22 7669056
1994 Human somatostatin receptor, SSTR2, is coupled to adenylyl cyclase in the presence of Gi alpha 1 protein. Biochemical and biophysical research communications 22 7914078
2012 Coexpression of human somatostatin receptor-2 (SSTR2) and SSTR3 modulates antiproliferative signaling and apoptosis. Journal of molecular signaling 21 22651821
1994 Immunological detection of isoforms of the somatostatin receptor subtype, SSTR2. Journal of neurochemistry 21 7518495
2016 SSTR2 promoter hypermethylation is associated with the risk and progression of laryngeal squamous cell carcinoma in males. Diagnostic pathology 20 26796520
2009 Tumoral prostate shows different expression pattern of somatostatin receptor 2 (SSTR2) and phosphotyrosine phosphatase SHP-1 (PTPN6) according to tumor progression. Advances in urology 20 19365586
2010 SSTR2-based reporters for assessing gene transfer into non-small cell lung cancer: evaluation using an intrathoracic mouse model. Human gene therapy 19 20653396
2021 Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [111In]In-DOTATATE Uptake in NET Cells. Cancers 17 34638389
2019 Preclinical evaluation of a dual sstr2 and integrin αvβ3-targeted heterodimer [68Ga]-NOTA-3PEG4-TATE-RGD. Bioorganic & medicinal chemistry 17 31540828
2021 SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target. Cancers 16 34638429
2014 Cytoplasmic expression of SSTR2 and 5 by immunohistochemistry and by RT/PCR is not associated with the pharmacological response to octreotide. Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion 16 25008035
2018 SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery. Acta neurochirurgica 15 29858948
2011 Evaluation of copper-64-labeled somatostatin agonists and antagonist in SSTr2-transfected cell lines that are positive and negative for p53: implications for cancer therapy. Nuclear medicine and biology 15 22056254
1995 Differential expression and regulation of SSTR2 messenger RNA in rat gastric antrum and corpus. The American journal of physiology 15 7485506
1999 Identification of distinct signalling pathways for somatostatin receptors SSTR1 and SSTR2 as revealed by microphysiometry. Cellular signalling 14 10405760
2022 Epigenetic-Like Stimulation of Receptor Expression in SSTR2 Transfected HEK293 Cells as a New Therapeutic Strategy. Cancers 13 35626117
2021 The Value of SSTR2 Receptor-Targeted PET/CT in Proton Irradiation of Grade I Meningioma. Cancers 13 34572933
2015 mRNA expression of somatostatin receptor subtypes SSTR-2, SSTR-3, and SSTR-5 and its significance in pancreatic cancer. World journal of surgical oncology 13 25890201
2012 Resistance to octreotide LAR in acromegalic patients with high SSTR2 expression: analysis of AIP expression. Arquivos brasileiros de endocrinologia e metabologia 13 23295289
2011 Somatostatin receptors SSTR2 and SSTR5 are expressed in the human thoracic duct. Lymphology 13 21667819
2005 Transfection of SSTR-1 and SSTR-2 inhibits Panc-1 cell proliferation and renders Panc-1 cells responsive to somatostatin analogue. Journal of the American College of Surgeons 13 16183496
2002 SSTR2 mediates the somatostatin-induced increase in intracellular Ca(2+) concentration and insulin secretion in the presence of arginine vasopressin in clonal beta-cell HIT-T15. Life sciences 13 12084389
2024 Cortistatin protects against septic cardiomyopathy by inhibiting cardiomyocyte pyroptosis through the SSTR2-AMPK-NLRP3 pathway. International immunopharmacology 12 38733824
2020 The role of somatostatin and its receptors (sstr2, sstr5) in the contractility of gilt inflamed uterus. Research in veterinary science 12 33002813
2017 Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma). Medical science monitor : international medical journal of experimental and clinical research 12 28434012
2010 Rainbow trout somatostatin receptor subtypes SSTR1A, SSTR1B, and SSTR2 differentially activate the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling pathways in transfected cells. Journal of molecular endocrinology 12 20732992
2024 Peptide-guided adaptor-CAR T-Cell therapy for the treatment of SSTR2-expressing neuroendocrine tumors. Oncoimmunology 11 39376579
2013 Association between polymorphisms in the P2RY1 and SSTR2 genes and sudden infant death syndrome. International journal of legal medicine 10 23828624
2007 A radioiodinated MIBG-octreotate conjugate exhibiting enhanced uptake and retention in SSTR2-expressing tumor cells. Bioconjugate chemistry 10 17979223
2023 Molecular simulations of SSTR2 dynamics and interaction with ligands. Scientific reports 9 36959237
2017 Occludin downregulation in high glucose is regulated by SSTR2 via the VEGF/NRP1/Akt signaling pathway in RF/6A cells. Experimental and therapeutic medicine 9 28810643
2020 Discovery and SAR Studies of Orally Active Somatostatin Receptor Subtype-2 (SSTR2) Agonists for the Treatment of Acromegaly. ACS chemical neuroscience 8 32315148
2021 A Cyanine-Bridged Somatostatin Hybrid Probe for Multimodal SSTR2 Imaging in Vitro and in Vivo: Synthesis and Evaluation. Chembiochem : a European journal of chemical biology 7 33238069
1999 A microplate binding assay for the somatostatin type-2 receptor (SSTR2). Journal of receptor and signal transduction research 7 10071756
2022 Synthesis and Evaluation of Two Long-Acting SSTR2 Antagonists for Radionuclide Therapy of Neuroendocrine Tumors. Pharmaceuticals (Basel, Switzerland) 6 36145375
2021 Synthesis and preliminary evaluation of octreotate conjugates of bioactive synthetic amatoxins for targeting somatostatin receptor (sstr2) expressing cells. RSC chemical biology 6 35128410
2010 Does the response of GH-secreting pituitary adenomas to octreotide depend on the cellular localization of the somatostatin receptor subtypes SSTR2 and SSTR5? Endokrynologia Polska 6 20464704
2025 PSMA and SSTR2 Dual-Targeting Theranostic Agents for Neuroendocrine-Differentiated Prostate Cancer (NEPC). Journal of medicinal chemistry 5 39791476
2024 Immunohistochemical Profiling of SSTR2 and HIF-2α with the Tumor Microenvironment in Pheochromocytoma and Paraganglioma. Cancers 5 38927897
2024 The heterobivalent (SSTR2/albumin) radioligand [67Cu]Cu-NODAGA-cLAB4-TATE enables efficient somatostatin receptor radionuclide theranostics. Theranostics 5 39310112
2022 SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity. Scientific reports 5 36463361
2018 Regional differences in somatostatin receptor 2 (SSTR2) immunoreactivity is coupled to level of bowel invasion in small intestinal neuroendocrine tumors. Neuro endocrinology letters 5 30531706
2014 Expression and localization of somatostatin receptor types 3, 4 and 5 in the wild-type, SSTR1 and SSTR1/SSTR2 knockout mouse cochlea. Cell and tissue research 5 25149275
2001 Association analysis of somatostatin receptor (SSTR1 and SSTR2) polymorphisms in breast cancer and solar keratosis. Cancer letters 5 11311492
2023 Applying HDACis to increase SSTR2 expression and radiolabeled DOTA-TATE uptake: from cells to mice. Life sciences 4 37907154
2009 Association of SSTR2 polymorphisms and glucose homeostasis phenotypes: the Insulin Resistance Atherosclerosis Family Study. Diabetes 4 19324939
2006 Inhibition of metastatic progression of SSTR2 gene transfection mediated by adenovirus in human pancreatic carcinoma cells. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 4 16711011
1995 Expression of sstr1 and sstr2 in rat hypothalamus: correlation with receptor binding and distribution of growth hormone regulatory peptides. Ciba Foundation symposium 4 7587644
2024 Preclinical Study of a Dual-Target Molecular Probe Labeled with 68Ga Targeting SSTR2 and FAP. Pharmaceuticals (Basel, Switzerland) 3 39770488
2010 [Expression of SSTR2 and P-STAT3 in human olfactory neuroblastoma]. Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery 3 20942237
2025 Characterizing SSTR2 expression and modulation for targeted imaging and therapy in preclinical models of triple-negative breast cancer. Scientific reports 2 40121305
2025 miR-375 Regulation of SSTR2 Expression in Corticotroph Pituitary Cells: Somatostatin Receptor Ligands Effects. Endocrinology 2 40488558
2023 Novel Discovery of the Somatostatin Receptor (SSTR2) in Pleomorphic Adenomas via Immunohistochemical Analysis of Tumors of the Salivary Glands. Cancers 2 37568733
2022 Immunohistochemical Expression Pattern of Theragnostic Targets SSTR2 and PSMA in Endolymphatic Sac Tumors: A Single Institution Case Series. Head and neck pathology 2 35546652