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Gene Review

Sstr2  -  somatostatin receptor 2

Rattus norvegicus

Synonyms: SRIF-1, SS-2-R, SS2-R, SS2R, Somatostatin receptor type 2
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Disease relevance of Sstr2

  • Attempts to use SRIF as an adjunct in the treatment of diabetes mellitus met with limited success due to its short biological half-life and the undesirable diabetogenic activity of its insulin-lowering properties [1].
  • These data suggest that SRIF receptors selectively couple to two G proteins, one of which is sparsely expressed in GH4C1 cells; the data conform to the notion that SRIF receptors discriminate between similar pertussis toxin-sensitive G proteins [2].
  • This is further indicated by studies on SRIF receptors in the pituitary tumor cell line, AtT-20 [3].
  • We have previously shown that [125I-Tyr11]SRIF binds to specific, high affinity receptors on RINm5F insulinoma cells and that these receptors mediate the action of SRIF to inhibit insulin release [4].
  • At present, the role played by hypersecretion of pancreatic SRIF in the obesity syndrome of the Zucker rat remains obscure [5].

Psychiatry related information on Sstr2


High impact information on Sstr2

  • Efforts at synthesis have yielded SRIF derivatives with prolonged GH-lowering activity which did not suppress glucagon or had equivalent insulin-inhibiting activity as well as several short-acting compounds with the appropriate glucagon specificity [1].
  • We report here that Wy-41, 747, unlike SRIF and other of its analogues tested, releases LH, induces ovulation and inhibits pregnancy when administered before or after implantation; these properties are traditionally associated with the separate LH-releasing class of peptides [1].
  • Insulin was infused for 120 min at rates of 1.5, 3, 6, 12, 24, and 108 pmol/kg per min in 24-h fasted rats and at rates of 3, 6, 9, 12, 36, and 108 pmol/kg per min in 6-h fasted rats while endogenous insulin release was inhibited by SRIF infusion and plasma glucose was maintained at the basal level [11].
  • Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and intracellular cyclic AMP accumulation to GRH, while somatostatin (SRIF) suppressive effects on GH secretion were increased [12].
  • T4Rx completely restored hypothalamic GRH content and spontaneous GH secretion despite only partial recovery of pituitary GH content, GRH and SRIF sensitivity, and intracellular cyclic AMP response to GRH [12].

Chemical compound and disease context of Sstr2

  • The retroenantiomer hexapeptide analog L363-572, which is 70-fold less potent than MK 678 to inhibit radioligand binding to SRIF1 receptors, did not affect locomotor activity at doses up to 100 ng/side [6].
  • This effect was mediated by SRIF1 receptors, as MK 678 (1-320 ng/side) produced a dose-dependent significant increase in locomotor activity with a maximal 228% increase relative to saline control, comparable to that attained with 3 to 10 micrograms of d-amphetamine [6].
  • Ba2+ current inhibitions by DAMGO and SRIF were attenuated by pertussis toxin pretreatment [13].
  • Our present studies suggest that rat hypothalamic SRIF release reflects ambient glucose status, is stimulated by glucopenia, and may explain inhibition of GH secretion in the rat during hypoglycemia [14].
  • To evaluate the action of SRIF and its analog octreotide on the proliferation and cell cycle kinetics of endocrine cells, we investigated their effect on GH3 rat pituitary tumor cells, a GH-producing cell line [15].

Biological context of Sstr2

  • Radioligand binding studies on rat colonic mucosal membranes using [125I]-Tyr11-SRIF suggested heterogeneity of SRIF binding sites [16].
  • Thus, SRIF and SRIF28 competed for binding (IC50 values, 0.32 and 0.63 nM, respectively) with Hill slopes less than unity; while seglitide and BIM-23027 both maximally displaced only 30-40% of specific binding with apparent high affinity (respective pIC50 values, 10.1 nM and 10.0) [16].
  • Under basal conditions, cumulative administration of SRIF and SRIF28 decreased short circuit current (SCC), a measure of electrogenic ion transport, with EC50 values of 4 nM and 9 nM respectively [16].
  • RESULTS: Polymerase chain reaction performed with templates from an ECL cell complementary DNA library and primers specific to each of the five known somatostatin receptor subtypes showed that the somatostatin receptor type 2 was significantly enriched in ECL complementary DNA [17].
  • In contrast to SRIF, only 5% of newly synthesized endogenous growth hormone was stored intracellularly, whereas 95% was sorted to the constitutive pathway and secreted rapidly with kinetics identical to proSRIF [18].

Anatomical context of Sstr2


Associations of Sstr2 with chemical compounds

  • The SRIF1 receptor is sensitive to cyclic hexapeptides such as MK-678 and to GTP gamma S but insensitive to smaller CGP-23996-like compounds [21].
  • 5. The sst2 receptor selective peptides, BIM-23027, seglitide and octreotide were the most potent inhibitors of gastrin-, dimaprit- and IBMX-induced acid secretion suggesting that SRIF receptors resembling the recombinant sst2 receptors are involved [22].
  • We have previously shown that exogenous SRIF potently stimulates striatal dopamine (DA) release via a glutamate-dependent mechanism [23].
  • 6 The AMPA/kainate receptor antagonist, DNQX (100 microM), abolished the agonist effects of BIM-23027 as previously shown for SRIF [23].
  • 4. The inhibitory effect of a range of SRIF analogues on gastrin-, dimaprit- and IBMX-induced acid secretion was also studied [22].

Physical interactions of Sstr2

  • The aim of this study was to examine the potencies of several recently identified selective somatostatin (SRIF)-receptor ligands as inhibitors of electrogenic ion transport in the rat distal colonic mucosa with the view to identifying the SRIF receptor type involved [16].
  • To test this hypothesis, we have visualized radiolabeled SRIF-binding sites and GRF immunoreactivity (ir) in adjacent sections of the hypothalamus, by combined radioautography and immunohistochemistry [24].
  • Somatostatin (SRIF) initiates its biological activities by interacting with five homologous G-protein-coupled receptor subtypes (sst(1--5)) [25].
  • 5. In the cerebral cortex the chronical GH injection induced an increase in the number of antagonist binding sites and a decrease of their affinity, while the similar SRIF treatment led to an increase of the binding affinity without any change of M-receptor capacity [26].

Co-localisations of Sstr2


Regulatory relationships of Sstr2


Other interactions of Sstr2

  • Somatostatin and the somatostatin receptor 2 are reciprocally controlled by calcineurin during cerebellar granule cell maturation [32].
  • The SRIF2 receptor is sensitive to the CGP-23996-like compounds and can be selectively labeled by 125I-CGP-23996 in the presence of high concentrations of the hexapeptides or GTP gamma S because, unlike the SRIF1 receptor, the SRIF2 receptor is insensitive to these agents [21].
  • Therefore, this study was undertaken to evaluate the effect of GRF and cGMP on SRIF mRNA and SRIF release in the periventricular nuclei of male rats in vitro [33].
  • It is likely that this pertussis toxin substrate is involved in signal transduction of SRIF on cAMP-dependent actions of VIP and cAMP-independent action of TRH [34].
  • However, NA fibers, while found to form pericellular arrays around NPY neurons and, to a lesser extent, around SRIF neurons, were seen to target VIP cortical cells with single terminal varicosities [35].

Analytical, diagnostic and therapeutic context of Sstr2

  • The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting [36].
  • Steady-state levels of SRIF mRNA were measured by an S1 nuclease protection assay using a 32P-labeled rat SRIF RNA probe [33].
  • First, we measured the intensity of SST(2A) immunoreactivity, using quantitative light microscopic immunocytochemistry, and levels of SST(2A) mRNA, using semiquantitative RT-PCR, under conditions of acute SRIF release blockade [37].
  • To structurally identify the carbohydrate components of SRIF receptors, solubilized rat brain SRIF receptors were subjected to lectin affinity chromatography [3].
  • In 11 perfusions, with SRIF at 10 ng./ml., IRG decreased more than IRI (-75.2 per cent IRG and -46.9 per cent IRI) [38].


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  2. Identification and quantification of Gi-type GTP-binding proteins that copurify with a pituitary somatostatin receptor. Luthin, D.R., Eppler, C.M., Linden, J. J. Biol. Chem. (1993) [Pubmed]
  3. Structural analysis and functional role of the carbohydrate component of somatostatin receptors. Rens-Domiano, S., Reisine, T. J. Biol. Chem. (1991) [Pubmed]
  4. The processing of receptor-bound [125I-Tyr11]somatostatin by RINm5F insulinoma cells. Sullivan, S.J., Schonbrunn, A. J. Biol. Chem. (1986) [Pubmed]
  5. Hypersection of pancreatic somatostatin in the obese Zucker rat: effects of food restriction and age. Trimble, E.R., Herberg, L., Renold, A.E. Diabetes (1980) [Pubmed]
  6. Somatostatin receptors in the nucleus accumbens selectively mediate the stimulatory effect of somatostatin on locomotor activity in rats. Raynor, K., Lucki, I., Reisine, T. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  7. Granulocyte-macrophage colony-stimulating factor modulates rapid eye movement (REM) sleep and non-REM sleep in rats. Kimura, M., Kodama, T., Aguila, M.C., Zhang, S.Q., Inoue, S. J. Neurosci. (2000) [Pubmed]
  8. Trophic effects of somatostatin on calcium flux: dynamic analysis and correlation with pituitary hormone release. Login, I.S., Judd, A.M. Endocrinology (1986) [Pubmed]
  9. Somatostatin release as measured by in vivo microdialysis: circadian variation and effect of prolonged food deprivation. Ishikawa, M., Mizobuchi, M., Takahashi, H., Bando, H., Saito, S. Brain Res. (1997) [Pubmed]
  10. Sleep deprivation increases somatostatin and growth hormone-releasing hormone messenger RNA in the rat hypothalamus. Toppila, J., Alanko, L., Asikainen, M., Tobler, I., Stenberg, D., Porkka-Heiskanen, T. Journal of sleep research. (1997) [Pubmed]
  11. Skeletal muscle glycogenolysis is more sensitive to insulin than is glucose transport/phosphorylation. Relation to the insulin-mediated inhibition of hepatic glucose production. Rossetti, L., Hu, M. J. Clin. Invest. (1993) [Pubmed]
  12. Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism. Katakami, H., Downs, T.R., Frohman, L.A. J. Clin. Invest. (1986) [Pubmed]
  13. Ca2+ channel and adenylyl cyclase modulation by cloned mu-opioid receptors in GH3 cells. Piros, E.T., Prather, P.L., Loh, H.H., Law, P.Y., Evans, C.J., Hales, T.G. Mol. Pharmacol. (1995) [Pubmed]
  14. Glucopenia-mediated release of somatostatin from incubated rat hypothalamus: monosaccharide specificity and role of glycolytic intermediates. Berelowitz, M., Ting, N.C., Murray, L. Endocrinology (1989) [Pubmed]
  15. Somatostatin-14 and its analog octreotide exert a cytostatic effect on GH3 rat pituitary tumor cell proliferation via a transient G0/G1 cell cycle block. Cheung, N.W., Boyages, S.C. Endocrinology (1995) [Pubmed]
  16. Somatostatin receptors mediating inhibition of basal and stimulated electrogenic ion transport in rat isolated distal colonic mucosa. McKeen, E.S., Feniuk, W., Humphrey, P.P. Naunyn Schmiedebergs Arch. Pharmacol. (1995) [Pubmed]
  17. The somatostatin receptor subtype on rat enterochromaffinlike cells. Prinz, C., Sachs, G., Walsh, J.H., Coy, D.H., Wu, S.V. Gastroenterology (1994) [Pubmed]
  18. Retrovirus-mediated expression of preprosomatostatin: posttranslational processing, intracellular storage, and secretion in GH3 pituitary cells. Stoller, T.J., Shields, D. J. Cell Biol. (1988) [Pubmed]
  19. Expression cloning of a rat brain somatostatin receptor cDNA. Kluxen, F.W., Bruns, C., Lübbert, H. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. Targeting sst2A receptor-expressing cells in the rat hypothalamus through in vivo agonist stimulation: neuroanatomical evidence for a major role of this subtype in mediating somatostatin functions. Csaba, Z., Simon, A., Helboe, L., Epelbaum, J., Dournaud, P. Endocrinology (2003) [Pubmed]
  21. Analogues of somatostatin bind selectively to brain somatostatin receptor subtypes. Raynor, K., Coy, D.C., Reisine, T. J. Neurochem. (1992) [Pubmed]
  22. Somatostatin sst2 receptor-mediated inhibition of parietal cell function in rat isolated gastric mucosa. Wyatt, M.A., Jarvie, E., Feniuk, W., Humphrey, P.P. Br. J. Pharmacol. (1996) [Pubmed]
  23. Evidence that somatostatin sst2 receptors mediate striatal dopamine release. Hathway, G.J., Humphrey, P.P., Kendrick, K.M. Br. J. Pharmacol. (1999) [Pubmed]
  24. Colocalization of somatostatin receptors and growth hormone-releasing factor immunoreactivity in neurons of the rat arcuate nucleus. McCarthy, G.F., Beaudet, A., Tannenbaum, G.S. Neuroendocrinology (1992) [Pubmed]
  25. Somatostatin receptor subtype 1 (sst(1)) regulates intracellular 3',5'-cyclic adenosine monophosphate accumulation in rat embryonic cortical neurons: evidence with L-797,591, an sst(1)-subtype-selective nonpeptidyl agonist. Blake, A.D. Neuropharmacology (2001) [Pubmed]
  26. Muscarinic receptor activity change after prolonged treatment with growth hormone and somatostatin. Popova, J., Robeva, A., Zaharieva, S. Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol. (1990) [Pubmed]
  27. Immunohistochemical markers in rat cortex: co-localization of calretinin and calbindin-D28k with neuropeptides and GABA. Rogers, J.H. Brain Res. (1992) [Pubmed]
  28. Growth hormone-releasing hormone neurons in the arcuate nucleus express both Sst1 and Sst2 somatostatin receptor genes. Tannenbaum, G.S., Zhang, W.H., Lapointe, M., Zeitler, P., Beaudet, A. Endocrinology (1998) [Pubmed]
  29. Somatostatin inhibits vasoactive intestinal peptide-stimulated cyclic adenosine monophosphate accumulation in GH pituitary cells. Dorflinger, L.J., Schonbrunn, A. Endocrinology (1983) [Pubmed]
  30. Stimulation of growth hormone secretion by central administration of atrial natriuretic polypeptide in the rat. Murakami, Y., Kato, Y., Tojo, K., Inoue, T., Yanaihara, N., Imura, H. Endocrinology (1988) [Pubmed]
  31. Somatostatin potentiates NMDA receptor function via activation of InsP(3) receptors and PKC leading to removal of the Mg(2+) block without depolarization. Pittaluga, A., Bonfanti, A., Raiteri, M. Br. J. Pharmacol. (2000) [Pubmed]
  32. Somatostatin and the somatostatin receptor 2 are reciprocally controlled by calcineurin during cerebellar granule cell maturation. Kramer, D., Caruso, A., Nicoletti, F., Genazzani, A.A. J. Neurochem. (2005) [Pubmed]
  33. Growth hormone-releasing factor increases somatostatin release and mRNA levels in the rat periventricular nucleus via nitric oxide by activation of guanylate cyclase. Aguila, M.C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  34. Pertussis toxin blocks the inhibitory effects of somatostatin on cAMP-dependent vasoactive intestinal peptide and cAMP-independent thyrotropin releasing hormone-stimulated prolactin secretion of GH3 cells. Yajima, Y., Akita, Y., Saito, T. J. Biol. Chem. (1986) [Pubmed]
  35. Noradrenergic innervation of peptidergic interneurons in the rat visual cortex. Paspalas, C.D., Papadopoulos, G.C. Cereb. Cortex (1999) [Pubmed]
  36. Development of antibodies against the rat brain somatostatin receptor. Theveniau, M., Rens-Domiano, S., Law, S.F., Rougon, G., Reisine, T. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  37. Somatostatin-induced regulation of SST(2A) receptor expression and cellsurface availability in central neurons: role of receptor internalization. Boudin, H., Sarret, P., Mazella, J., Schonbrunn, A., Beaudet, A. J. Neurosci. (2000) [Pubmed]
  38. Reversal of somatostatin inhibition of insulin and glucagon secretion. Bhathena, S.J., Perrino, P.V., Voyles, N.R., Smith, S.S., Wilkins, S.D., Coy, D.H., Schally, A.V., Recant, L. Diabetes (1976) [Pubmed]
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