Affinage

SSTR2

Somatostatin receptor type 2 · UniProt P30874

Length
369 aa
Mass
41.3 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SSTR2 is a Gi/Go-coupled somatostatin receptor that transduces somatostatin signals into inhibition of secretion, growth, and metabolic output across endocrine, gastrointestinal, and pituitary tissues (PMID:8098703, PMID:8096694, PMID:7907016, PMID:8144617, PMID:22932785). It selectively associates with pertussis toxin-sensitive Gi alpha 3 and Go alpha subunits and inhibits adenylyl cyclase, an effect that depends on the available Gi pool (PMID:8098703, PMID:8096694, PMID:7907016, PMID:8144617, PMID:7914078). Beyond cAMP suppression, SSTR2 activates a tyrosine phosphatase that mediates its antiproliferative signal—mechanistically distinct from the Ca2+-based growth inhibition of SSTR5—and engages phospholipase C/Ca2+ mobilization through partially PTX-insensitive pathways that require receptor regions beyond the intracellular loops (PMID:7907795, PMID:7878022, PMID:9228036). SSTR2 also couples to inhibition of high-voltage-activated and L-type Ca2+ channels and, in human islet cells, suppresses insulin/glucagon secretion through GIRK channel activation, reduction of P/Q-type Ca2+ currents, and direct inhibition of exocytosis (PMID:7982482, PMID:8684611, PMID:22932785). Ligand selectivity is encoded by specific transmembrane residues: Asp122 (TM III) forms an ionic contact with somatostatin Lys9, while Gln291 (TM VI) and Ser305 (TM VII) determine high-affinity peptide agonist recognition (PMID:7882976, PMID:7488212). At the plasma membrane, transient interactions with filamin A along actin fibers control SSTR2 nanoscale clustering and clathrin-mediated internalization (PMID:29931263). Tissue-level roles include suppression of pituitary hormone release, regulation of ductal bile homeostasis via cGMP and cAMP, and control of gastric acid secretion through expression on parietal and ECL cells (PMID:9045884, PMID:12442323, PMID:12676656). SSTR2 abundance is regulated post-transcriptionally by glucocorticoid-induced miR-375, which limits receptor expression and dampens octreotide responsiveness (PMID:40488558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Established the G protein coupling specificity of SSTR2, defining which transducers carry its signal and distinguishing it from related receptors.

    Evidence Subtype-specific G protein antisera immunoprecipitation in CHO and HEK293 cells, plus cAMP accumulation assays in transfected CHO cells

    PMID:7907016 PMID:8096694 PMID:8098703 PMID:8144617

    Open questions at the time
    • Stoichiometry and dynamics of Gi alpha 3/Go alpha selection not resolved
    • Did not address PTX-insensitive coupling later observed for PLC
  2. 1994 High

    Resolved that adenylyl cyclase inhibition by SSTR2 depends on the available Gi alpha subunit pool, explaining cell-context dependence of cAMP responses.

    Evidence Co-expression of SSTR2 with individual Gi alpha subunits in Gi alpha 1-deficient CHO cells with PTX controls

    PMID:7914078

    Open questions at the time
    • Reconciliation with the earlier Gi alpha 3/Go alpha association data not addressed
    • Single lab, single cell background
  3. 1994 High

    Identified tyrosine phosphatase activation as the transducer of SSTR2 growth inhibition, separating its antiproliferative mechanism from second-messenger pathways.

    Evidence Tyrosine phosphatase and proliferation assays with selective analogues in COS-7, NIH 3T3 and CHO cells; orthovanadate suppression

    PMID:7878022 PMID:7907795

    Open questions at the time
    • Identity of the specific phosphatase not established
    • Downstream substrates of the phosphatase unknown
  4. 1994 Medium

    Demonstrated SSTR2 couples to PLC/Ca2+ and to Ca2+ channel inhibition, broadening its effector repertoire beyond cAMP and showing subtype-specific channel control.

    Evidence Inositol phosphate/Ca2+ measurements with PTX in COS-7 cells; patch-clamp of HVA Ca2+ currents in RINm5F cells expressing SSTR2 versus SSTR1

    PMID:7910018 PMID:7982482 PMID:9228036

    Open questions at the time
    • Identity of the PTX-insensitive G protein driving PLC not defined
    • Link between PLC and channel effects not integrated
  5. 1995 High

    Mapped the molecular determinants of somatostatin ligand recognition, defining how SSTR2 achieves selective high-affinity binding.

    Evidence Site-directed and charge-swap mutagenesis of SSTR1/SSTR2 (Asp122, Gln291, Ser305) with radioligand binding

    PMID:7488212 PMID:7882976

    Open questions at the time
    • No experimental structure of the ligand-bound receptor
    • Contribution of these residues to downstream signaling not tested
  6. 1995 High

    Showed SSTR2 and SSTR5 use mechanistically distinct growth-inhibition pathways (phosphatase vs Ca2+), clarifying subtype division of labor.

    Evidence Isogenic CHO lines expressing each SSTR subtype with phosphatase inhibitor and Ca2+ readouts

    PMID:7878022

    Open questions at the time
    • Molecular link from phosphatase to cell-cycle arrest not defined
  7. 1997 High

    Established that SSTR2 PLC coupling requires receptor regions beyond the third intracellular loop, refining the structural basis of effector engagement.

    Evidence SSTR1/SSTR2 chimeric receptors in pituitary F4C1/GH12C1 cells with cAMP, PLC and Ca2+ readouts under PTX

    PMID:9228036

    Open questions at the time
    • Specific extra-loop determinants not pinpointed
    • G protein mediating PTX-resistant PLC not identified
  8. 1997 High

    Assigned SSTR2 a defined role in pituitary hormone suppression, linking the receptor to specific endocrine outputs.

    Evidence Primary human fetal pituitary cultures with subtype-selective analogues correlated to binding affinities

    PMID:9045884

    Open questions at the time
    • Downstream signaling in pituitary cells not dissected here
  9. 2003 High

    Defined tissue-specific physiological roles for SSTR2 in gastrointestinal and biliary function using genetic models.

    Evidence LacZ knockin reporter mice for GI cell-type mapping; isolated bile duct units from SSTR2 knockout mice with cAMP/cGMP readouts

    PMID:12442323 PMID:12676656

    Open questions at the time
    • Cell-autonomous signaling steps in cholangiocytes not fully traced
    • Parietal/ECL cell signaling consequences not quantified
  10. 2012 High

    Established SSTR2 as the dominant islet receptor inhibiting hormone secretion through three parallel ionic and exocytotic mechanisms.

    Evidence Human islets with patch-clamp (GIRK, P/Q Ca2+ currents), exocytosis and secretion assays using subtype-selective agonists

    PMID:12084389 PMID:22932785

    Open questions at the time
    • G protein/effector links to each ionic mechanism not fully resolved
  11. 2018 High

    Revealed how SSTR2 spatial organization and internalization are controlled at the membrane, linking a cytoskeletal partner to receptor trafficking.

    Evidence Single-molecule live-cell microscopy with dominant-negative filamin A fragment tracking SSTR2 clustering and CCP recruitment

    PMID:29931263

    Open questions at the time
    • Binding interface between SSTR2 and FLNA not mapped
    • Functional consequence of altered clustering on signaling not measured
  12. 2025 Medium

    Identified post-transcriptional control of SSTR2 abundance by glucocorticoid-induced miR-375, explaining modulation of therapeutic agonist responsiveness.

    Evidence miR-375 inhibitor with protein/internalization and antiproliferative readouts in AtT20/D16 cells and primary human corticotroph cultures

    PMID:40488558

    Open questions at the time
    • Direct miR-375/Sstr2 mRNA interaction site not validated
    • Single lab
  13. 2024 Medium

    Extended SSTR2 signaling to an AMPK/Drp1 axis controlling mitochondrial fission and inflammasome-driven pyroptosis in cardiac stress.

    Evidence Sepsis mouse model with SSTR2 pharmacological inhibition and genetic ablation; AMPK, Drp1, caspase-1 and cardiac function readouts

    PMID:38733824

    Open questions at the time
    • Proximal coupling from SSTR2 to AMPK not defined
    • Single lab; cell-type specificity in heart unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple SSTR2 effector arms (phosphatase, PLC, ion channels, AMPK) are integrated and selectively engaged in a given cell type, and the structural basis of effector versus FLNA coupling, remain open.
  • No unified structural model of ligand-bound, G protein-coupled SSTR2
  • Mechanism selecting among parallel effector pathways unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3
Partners
FLNAGNAI3GNAO1

Evidence

Reading pass · 23 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 pertussis toxin-sensitive G proteins, as demonstrated by immunoprecipitation with peptide-directed antisera in CHO cells expressing the cloned receptor; Gi alpha 1 and Gi alpha 2 antisera did not uncouple SSTR2/G protein complexes. Immunoprecipitation with subtype-specific G protein antisera in CHO and HEK293 cells stably expressing SSTR2 The Journal of biological chemistry High 8098703
1993 Rat SSTR2 expressed in CHO cells is coupled to inhibition of adenylyl cyclase: somatostatin-14 inhibited forskolin-stimulated cAMP accumulation by ~75% with EC50 ~350 pM. cAMP accumulation assay in CHO cells stably transfected with rat SSTR2 cDNA Biochemical and biophysical research communications High 7907016 8096694 8144617
1994 SSTR2 activation stimulates tyrosine phosphatase activity and inhibits serum-stimulated cell proliferation (EC50 in low pM range for RC-160 and SMS 201-995), implicating tyrosine phosphatase as a transducer of the SSTR2 growth-inhibition signal. Tyrosine phosphatase activity assay and cell proliferation assay in COS-7 and NIH 3T3 cells expressing human SSTR2; pharmacological dose-response with selective analogues Proceedings of the National Academy of Sciences of the United States of America High 7878022 7907795
1994 SSTR2 couples to phospholipase C and Ca2+ mobilization in addition to inhibiting adenylyl cyclase; the PLC/Ca2+ response is only partially sensitive to pertussis toxin, indicating involvement of both PTX-sensitive and PTX-insensitive G proteins. Transfection of human SSTR2 cDNA into COS-7 cells; measurement of cAMP, inositol phosphates, and intracellular Ca2+ with pertussis toxin treatment Biochemical and biophysical research communications Medium 7910018 9228036
1994 SSTR2 coupling to adenylyl cyclase inhibition requires the presence of Gi alpha 1 protein: human SSTR2 in CHO cells (which lack Gi alpha 1) does not inhibit cAMP unless Gi alpha 1 is co-expressed; the effect is pertussis toxin-sensitive. Co-expression of human SSTR2 with individual Gi alpha subunits in CHO cells; cAMP assay with pertussis toxin Biochemical and biophysical research communications High 7914078
1994 SSTR2 inhibits high-voltage-activated (HVA) Ca2+ currents in RINm5F insulinoma cells; SSTR1 expressed in the same cells does not inhibit these currents, demonstrating subtype specificity. Patch-clamp electrophysiology in RINm5F cells stably expressing human SSTR2 or SSTR1 FEBS letters High 7982482
1994 SSTR2 couples exclusively to pertussis toxin-sensitive G proteins (evidenced by GTPγS and PTX effects on ligand binding), whereas SSTR1 couples to both PTX-sensitive and -insensitive G proteins; only SSTR1, not SSTR2, mediates somatostatin inhibition of Na+-H+ exchange activity via a PTX-insensitive mechanism. Stable/transient expression of SSTR1, SSTR2, and chimeric receptors in Ltk- and HEK293 cells; Na+-H+ exchange assay, cAMP assay, pertussis toxin treatment, chimeric receptor mapping The Journal of biological chemistry High 8144617
1995 Two amino acids in transmembrane domains VI (Gln291→Asn) and VII (Ser305→Phe) of SSTR2 largely determine the high-affinity selectivity of the peptide agonist SMS 201-995; single Ser305→Phe mutation in SSTR1 increases SMS 201-995 affinity ~100-fold, and combining with Gln291→Asn yields near-full SMS 201-995 susceptibility. Site-directed mutagenesis of SSTR1 with sequential introduction of SSTR2 residues; radioligand binding assays The EMBO journal High 7882976
1995 Asp122 in transmembrane domain III of SSTR2 is a critical contact residue for somatostatin-14 binding: charge-switch mutations (D122K receptor + asp9-S-14 ligand) restore binding, implicating an ionic interaction between Lys9 of S-14 and Asp122 of SSTR2. Site-directed mutagenesis of rat SSTR2 (D89A, D89E, D122K); radioligand binding with wild-type and charge-substituted somatostatin analogues Biochemical and biophysical research communications High 7488212
1995 SSTR2-mediated inhibition of cell proliferation acts through tyrosine phosphatase activation (suppressed by orthovanadate), whereas SSTR5-mediated growth inhibition operates through inhibition of intracellular Ca2+ mobilization (not through the phosphatase pathway); distinct mechanisms for each subtype. CHO cells stably expressing individual SSTR subtypes 1–5; proliferation assays with orthovanadate and phosphatase inhibitors; intracellular calcium measurements Proceedings of the National Academy of Sciences of the United States of America High 7878022
1996 SSTR2 couples to inhibition of L-type Ca2+ channels in AtT-20 pituitary cells via pertussis toxin-sensitive G proteins; this coupling is not desensitized by SSTR2-selective agonist pretreatment (unlike SSTR5, which undergoes desensitization). Whole-cell patch-clamp in AtT-20 cells; SSTR2-selective agonists (MK 678, BIM 23027, NC8-12); pertussis toxin pretreatment Neuroscience High 8684611
1994 SSTR2 protein migrates at 93 kDa in CHO cells expressing the cloned receptor and at 148 kDa in rat brain regions with high SSTR2 mRNA, indicating differential post-translational modification (likely glycosylation) in native tissue versus transfected cells. Peptide-directed antibody immunoblotting and immunoprecipitation of SSTR2 from transfected CHO cells and rat brain Journal of neurochemistry Medium 7518495
1995 SSTR2 activation in AR42J pancreatic cells opens cell-surface calcium channels in a phospholipase C-independent manner: SSTR2-selective agonists increase intracellular Ca2+ that is abolished in Ca2+-free medium but do not stimulate inositol phosphate turnover. Intracellular Ca2+ measurement and inositol phosphate assay in AR42J cells using SSTR subtype-selective agonists Biochemical and biophysical research communications Medium 7669056
1997 SSTR2 activation in pituitary F4C1 cells stimulates phospholipase C and raises intracellular Ca2+ from intracellular stores (partially PTX-resistant); sequences beyond the intracellular loops—not only the third intracellular loop—are required for SSTR2 coupling to PLC, as chimeras containing only SSTR2 intracellular loops in SSTR1 background did not reconstitute PLC stimulation. Expression of SSTR1, SSTR2, and chimeric receptors in pituitary GH12C1 and F4C1 cells; adenylyl cyclase inhibition, PLC activity, and [Ca2+]i measurements with pertussis toxin The Journal of biological chemistry High 9228036
1997 In human fetal pituitary cells, prolactin suppression is mediated predominantly by SSTR2, whereas GH and TSH suppression are mediated by both SSTR2 and SSTR5, as shown by subtype-selective somatostatin analogues with defined binding affinities. Primary human fetal pituitary cultures treated with SSTR2- or SSTR5-selective analogues; hormone secretion assays correlated with receptor binding affinities in stably transfected cell lines The Journal of clinical investigation High 9045884
2002 In the gastrointestinal tract, SSTR2 is expressed on parietal cells and enterochromaffin-like (ECL) cells in the stomach, and on NOS-positive neurons in the myenteric and submucosal plexuses of the intestine, as identified using Sstr2 knockout/lacZ knockin mice. LacZ knockin reporter mice; beta-galactosidase staining combined with immunostaining for H+K+ATPase (parietal cells), histidine decarboxylase (ECL cells), and NOS The Journal of comparative neurology High 12442323
2003 SSTR2 on cholangiocytes mediates somatostatin-induced stimulation of ductal bile absorption and inhibition of secretin-stimulated ductal bile secretion; these effects involve increases in intracellular cGMP and inhibition of secretin-stimulated cAMP, and are absent in SSTR2 knockout mice. Isolated intrahepatic bile duct units from wild-type and SSTR2 knockout mice; luminal area measurement, cAMP and cGMP assays, SSTR2-selective agonist L-779976 American journal of physiology. Cell physiology High 12676656
2012 In human pancreatic β- and α-cells, SSTR2 is the dominant somatostatin receptor mediating SST-induced inhibition of secretion through: (1) activation of GIRK channels causing membrane hyperpolarization, (2) reduction of P/Q-type Ca2+ currents, and (3) direct inhibition of exocytosis; SSTR5 is only marginally effective. Human islets: quantitative PCR, immunohistochemistry, whole-cell patch-clamp (GIRK channel blocker tertiapin-Q, tolbutamide), Ca2+ current recordings, exocytosis measurements with SSTR subtype-selective agonists American journal of physiology. Endocrinology and metabolism High 22932785
2018 SSTR2 undergoes transient interactions with the cytoskeletal protein filamin A (FLNA) preferentially along actin fibers; agonist stimulation increases SSTR2 localization along actin fibers, clustering, and recruitment to clathrin-coated pits (CCPs). Blocking SSTR2-FLNA binding with a dominant-negative FLNA fragment increases SSTR2 mobility, disrupts clustering along actin, and impairs both recruitment to CCPs and receptor internalization. Fast multicolor single-molecule microscopy in living cells; dominant-negative FLNA fragment; tracking of individual SSTR2 and FLNA molecules at the plasma membrane Endocrinology High 29931263
2002 In HIT-T15 clonal beta-cells, SSTR2 (not SSTR1, 3, 4, or 5) specifically mediates somatostatin-induced increase in intracellular Ca2+ and insulin secretion in the presence of arginine vasopressin; this effect is blocked by the SSTR2-specific antagonist PRL-2903. Subtype-selective SSTR agonists and SSTR2 antagonist PRL-2903; intracellular Ca2+ measurement and insulin secretion assay in HIT-T15 cells Life sciences Medium 12084389
2024 Cortistatin binds specifically to SSTR2 and activates AMPK, which inhibits Drp1-mediated mitochondrial fission, reduces ROS, and thereby suppresses NLRP3 inflammasome activation and cardiomyocyte pyroptosis in septic cardiomyopathy; pharmacological inhibition and genetic ablation of SSTR2 abolish these protective effects. Sepsis mouse model; SSTR2 pharmacological inhibition and genetic ablation; AMPK phosphorylation, Drp1 activity, caspase-1 cleavage, IL-1β, gasdermin D, and cardiac function measurements International immunopharmacology Medium 38733824
2006 SSTR2 overexpression in SSTR2-negative pancreatic carcinoma cells (BXPC-3) reduces cell migration and invasion through Matrigel, accompanied by reduced MMP-2 mRNA and increased TIMP-2 mRNA expression. Adenovirus-mediated SSTR2 transfection in BXPC-3 cells; Matrigel-coated Transwell migration/invasion assay; RT-PCR for MMP-2 and TIMP-2 Journal of Huazhong University of Science and Technology. Medical sciences Low 16711011
2025 miR-375 epigenetically downregulates SSTR2 expression in corticotroph pituitary cells: glucocorticoid (dexamethasone) treatment increases miR-375, which targets Sstr2 mRNA; miR-375 inhibition increases SSTR2 membranous protein expression, enhances receptor internalization upon octreotide treatment, and potentiates octreotide-induced antiproliferative and apoptotic effects (PARP cleavage, caspase-3, ERK1/2 phosphorylation). RT-qPCR, Western blot, immunofluorescence, miR-375 inhibitor, proliferation assay, flow cytometry in AtT20/D16 cells and primary human corticotroph cultures 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 280 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 267 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 133 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 109 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 64 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
2003 Somatostatin stimulates ductal bile absorption and inhibits ductal bile secretion in mice via SSTR2 on cholangiocytes. American journal of physiology. Cell physiology 48 12676656
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
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
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 45 38048045
2019 Discovery of an SSTR2-Targeting Maytansinoid Conjugate (PEN-221) with Potent Activity in Vitro and in Vivo. Journal of medicinal chemistry 45 30735385
2017 DNA methylation of CMTM3, SSTR2, and MDFI genes in colorectal cancer. Gene 42 28782576
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 42 11472428
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
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
2020 Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy. Cancer gene therapy 36 32684623
1997 Both overlapping and distinct signaling pathways for somatostatin receptor subtypes SSTR1 and SSTR2 in pituitary cells. The Journal of biological chemistry 35 9228036
2013 Inhibition of tumor promoting signals by activation of SSTR2 and opioid receptors in human breast cancer cells. Cancer cell international 34 24059654
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
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
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 26 37788300
2009 Somatostatin analogues inhibit cancer cell proliferation in an SSTR2-dependent manner via both cytostatic and cytotoxic pathways. Oncology reports 26 19148511
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 25 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
1994 Human somatostatin receptor, SSTR2, is coupled to adenylyl cyclase in the presence of Gi alpha 1 protein. Biochemical and biophysical research communications 24 7914078
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
2012 Coexpression of human somatostatin receptor-2 (SSTR2) and SSTR3 modulates antiproliferative signaling and apoptosis. Journal of molecular signaling 22 22651821
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
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 21 19365586
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
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 18 34638389
2019 Preclinical evaluation of a dual sstr2 and integrin αvβ3-targeted heterodimer [68Ga]-NOTA-3PEG4-TATE-RGD. Bioorganic & medicinal chemistry 18 31540828
2021 SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target. Cancers 16 34638429
2018 SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery. Acta neurochirurgica 16 29858948
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
2024 Cortistatin protects against septic cardiomyopathy by inhibiting cardiomyocyte pyroptosis through the SSTR2-AMPK-NLRP3 pathway. International immunopharmacology 15 38733824
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
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
2024 The heterobivalent (SSTR2/albumin) radioligand [67Cu]Cu-NODAGA-cLAB4-TATE enables efficient somatostatin receptor radionuclide theranostics. Theranostics 7 39310112
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
2023 Applying HDACis to increase SSTR2 expression and radiolabeled DOTA-TATE uptake: from cells to mice. Life sciences 6 37907154
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
2025 Characterizing SSTR2 expression and modulation for targeted imaging and therapy in preclinical models of triple-negative breast cancer. Scientific reports 5 40121305
2025 Upregulation of SSTR2 Expression and Radioligand Binding of [18F]SiTATE in Neuroendocrine Tumour Cells with Combined Inhibition of Class I HDACs and LSD1. Neuroendocrinology 5 40188826
2024 Immunohistochemical Profiling of SSTR2 and HIF-2α with the Tumor Microenvironment in Pheochromocytoma and Paraganglioma. Cancers 5 38927897
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
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
2025 miR-375 Regulation of SSTR2 Expression in Corticotroph Pituitary Cells: Somatostatin Receptor Ligands Effects. Endocrinology 3 40488558
2024 The Value of PET/CT in Particle Therapy Planning of Various Tumors with SSTR2 Receptor Expression: Comparative Interobserver Study. Cancers 3 38791956
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

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