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Gene Review

SSTR5  -  somatostatin receptor 5

Homo sapiens

Synonyms: SS-5-R, SS5-R, SS5R, Somatostatin receptor type 5
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Disease relevance of SSTR5


Psychiatry related information on SSTR5


High impact information on SSTR5

  • Selective nonpeptide agonists with nanomolar affinity have been developed for four of the subtypes (SSTR1, 2, 3, and 4) and putative peptide antagonists for SSTR2 and SSTR5 have been identified [6].
  • Analogue affinities determined by membrane radioligand binding in cells stably expressing human SSTR forms were either SSTR2 or SSTR5-selective [1].
  • An SSTR5-specific analog also exclusively inhibited GH in acromegalic tumor cells [7].
  • Luteinizing hormone was modestly decreased (15-20%) by SSTR2- or SSTR5-specific analogs [7].
  • In addition, in SSTR5-expressing cells, RC-160 inhibited CCK-stimulated intracellular calcium mobilization at doses (EC50, 0.35 nM) similar to those necessary to inhibit somatostatin-14 binding (IC50, 21 nM) and CCK-induced cell proliferation (EC50, 1.1 nM) [8].

Chemical compound and disease context of SSTR5


Biological context of SSTR5

  • Whereas growth inhibition has been reported to follow stimulation of protein tyrosine phosphatase via SSTR2 or inhibition of Ca2+ channels via SSTR5 in heterologous expression systems, the subtype selectivity for signaling apoptosis has not been investigated [12].
  • Swapping the C-tail of hSSTR1 with that of hSSTR5 induced internalization (27%) but not up-regulation [13].
  • C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest [14].
  • Using a combination of polymerase chain reaction and genomic library screening we have cloned a human gene for a subtype of the somatostatin (SST) receptor (SSTR) termed human SSTR5 (hSSTR5), which is located on chromosome 16 [4].
  • In this study we systematically screened the promoter and coding region of the SSTR5 gene for genetic variation that could contribute to the development of neuropsychiatric disorders [5].

Anatomical context of SSTR5


Associations of SSTR5 with chemical compounds

  • Glucose-stimulated insulin secretion in human islets incubated for 1 hr at 20 mM glucose, and in islets cultured for 24 hr at a near-physiological (6.1 mM) glucose concentration, was inhibited (<50% of the control) by SSTR5-specific analogs and by SS14 and SS28 [19].
  • Octreotide binds with greatest affinity to SSTR2 and SSTR5 [20].
  • The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding [21].
  • Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine D2 receptor and the SSTR5 receptor interact to form a receptor complex with enhanced functional activity [22].
  • This suggests that the inositol phospholipid/calcium pathway could be involved in the antiproliferative effect of RC-160 mediated by SSTR5 in these cells [8].

Physical interactions of SSTR5

  • In contrast, SSTR5 bound very few SRIF analogues with high affinity [23].
  • The multi-domain protein PIST (protein interacting specifically with Tc10) interacts with the SSTR5 (somatostatin receptor 5) and is responsible for its intracellular localization [24].

Regulatory relationships of SSTR5


Other interactions of SSTR5

  • Although hSSTR5 displays approximately 75% sequence identity with rat SSTR5, the two receptors display significantly different pharmacological profiles, especially with respect to their binding affinities for the SST analogue SMS 201-995 [4].
  • SSTR3, SSTR4, and SSTR5 mRNA was also dramatically increased at 24 and 48 hr [28].
  • Heterologous analogue combinations containing both SSTR2- and SSTR5-selective compounds were more potent in decreasing GH than analogues used alone (P < 0.05), or than combinations of compounds specific for the same receptor subtype (P < 0.005) [1].
  • Recent evidence shows that the dopamine D2 receptor (DRD2) and SSTR5 interact physically to form heterodimers with enhanced functional activity [5].
  • In the presence of S-Ab, infusion of the SSTR5 agonist had no significant effect on insulin or IAPP secretion [29].

Analytical, diagnostic and therapeutic context of SSTR5


  1. Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. Shimon, I., Yan, X., Taylor, J.E., Weiss, M.H., Culler, M.D., Melmed, S. J. Clin. Invest. (1997) [Pubmed]
  2. Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. Kubota, A., Yamada, Y., Kagimoto, S., Shimatsu, A., Imamura, M., Tsuda, K., Imura, H., Seino, S., Seino, Y. J. Clin. Invest. (1994) [Pubmed]
  3. Cortistatin inhibits growth hormone release from human fetal and adenoma pituitary cells and prolactin secretion from cultured prolactinomas. Rubinfeld, H., Hadani, M., Barkai, G., Taylor, J.E., Culler, M.D., Shimon, I. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  4. Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28. Panetta, R., Greenwood, M.T., Warszynska, A., Demchyshyn, L.L., Day, R., Niznik, H.B., Srikant, C.B., Patel, Y.C. Mol. Pharmacol. (1994) [Pubmed]
  5. Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with bipolar affective disorder. Nyegaard, M., Børglum, A.D., Bruun, T.G., Collier, D.A., Russ, C., Mors, O., Ewald, H., Kruse, T.A. Mol. Psychiatry (2002) [Pubmed]
  6. Somatostatin and its receptor family. Patel, Y.C. Frontiers in neuroendocrinology. (1999) [Pubmed]
  7. Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. Shimon, I., Taylor, J.E., Dong, J.Z., Bitonte, R.A., Kim, S., Morgan, B., Coy, D.H., Culler, M.D., Melmed, S. J. Clin. Invest. (1997) [Pubmed]
  8. Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Buscail, L., Estève, J.P., Saint-Laurent, N., Bertrand, V., Reisine, T., O'Carroll, A.M., Bell, G.I., Schally, A.V., Vaysse, N., Susini, C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  9. Expression of somatostatin receptor (SSTR) subtypes in pituitary adenomas: quantitative analysis of SSTR2 mRNA by reverse transcription-polymerase chain reaction. Murabe, H., Shimatsu, A., Ihara, C., Mizuta, H., Nakamura, Y., Nagata, I., Kikuchi, H., Nakao, K. J. Neuroendocrinol. (1996) [Pubmed]
  10. Thyroid hormone-induced expression of specific somatostatin receptor subtypes correlates with involution of the TtT-97 murine thyrotrope tumor. James, R.A., Sarapura, V.D., Bruns, C., Raulf, F., Dowding, J.M., Gordon, D.F., Wood, W.M., Ridgway, E.C. Endocrinology (1997) [Pubmed]
  11. Somatostatin receptor-specific analogs: effects on cell proliferation and growth hormone secretion in human somatotroph tumors. Danila, D.C., Haidar, J.N., Zhang, X., Katznelson, L., Culler, M.D., Klibanski, A. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  12. Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Sharma, K., Patel, Y.C., Srikant, C.B. Mol. Endocrinol. (1996) [Pubmed]
  13. Agonist-dependent up-regulation of human somatostatin receptor type 1 requires molecular signals in the cytoplasmic C-tail. Hukovic, N., Rocheville, M., Kumar, U., Sasi, R., Khare, S., Patel, Y.C. J. Biol. Chem. (1999) [Pubmed]
  14. C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest. Sharma, K., Patel, Y.C., Srikant, C.B. Mol. Endocrinol. (1999) [Pubmed]
  15. Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines. Ain, K.B., Taylor, K.D., Tofiq, S., Venkataraman, G. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  16. Developmental changes in the expression of somatostatin receptors (1-5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus. Goodyer, C.G., Grigorakis, S.I., Patel, Y.C., Kumar, U. Neuroscience (2004) [Pubmed]
  17. 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. Talme, T., Ivanoff, J., Hägglund, M., Van Neerven, R.J., Ivanoff, A., Sundqvist, K.G. Clin. Exp. Immunol. (2001) [Pubmed]
  18. Expression pattern of somatostatin receptor subtypes 1-5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis. Hagstr??mer, L., Emtestam, L., Stridsberg, M., Talme, T. Exp. Dermatol. (2006) [Pubmed]
  19. Inhibition of human pancreatic islet insulin release by receptor-selective somatostatin analogs directed to somatostatin receptor subtype 5. Zambre, Y., Ling, Z., Chen, M.C., Hou, X., Woon, C.W., Culler, M., Taylor, J.E., Coy, D.H., Van Schravendijk, C., Schuit, F., Pipeleers, D.G., Eizirik, D.L. Biochem. Pharmacol. (1999) [Pubmed]
  20. Distribution and functional significance of somatostatin receptors in malignant melanoma. Lum, S.S., Fletcher, W.S., O'Dorisio, M.S., Nance, R.W., Pommier, R.F., Caprara, M. World journal of surgery. (2001) [Pubmed]
  21. High expression of somatostatin receptors and messenger ribonucleic acid for its receptor subtypes in organ-confined and locally advanced human prostate cancers. Halmos, G., Schally, A.V., Sun, B., Davis, R., Bostwick, D.G., Plonowski, A. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  22. Analysis of transmission of novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene in patients with autism. Lauritsen, M.B., Nyegaard, M., Betancur, C., Colineaux, C., Josiassen, T.L., Kruse, T.A., Leboyer, M., Ewald, H. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
  23. Characterization of cloned somatostatin receptors SSTR4 and SSTR5. Raynor, K., O'Carroll, A.M., Kong, H., Yasuda, K., Mahan, L.C., Bell, G.I., Reisine, T. Mol. Pharmacol. (1993) [Pubmed]
  24. The PDZ/coiled-coil domain containing protein PIST modulates insulin secretion in MIN6 insulinoma cells by interacting with somatostatin receptor subtype 5. Wente, W., Efanov, A.M., Treinies, I., Zitzer, H., Gromada, J., Richter, D., Kreienkamp, H.J. FEBS Lett. (2005) [Pubmed]
  25. Somatostatin receptors in pituitary and development of somatostatin receptor subtype-selective analogs. Shimon, I. Endocrine (2003) [Pubmed]
  26. Phospholipase C activation and Ca2+ mobilization by cloned human somatostatin receptor subtypes 1-5, in transfected COS-7 cells. Akbar, M., Okajima, F., Tomura, H., Majid, M.A., Yamada, Y., Seino, S., Kondo, Y. FEBS Lett. (1994) [Pubmed]
  27. Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists, inhibits calcitonin secretion and gene expression in the human medullary thyroid carcinoma cell line, TT. Zatelli, M.C., Tagliati, F., Taylor, J.E., Piccin, D., Culler, M.D., degli Uberti, E.C. Horm. Metab. Res. (2002) [Pubmed]
  28. Somatostatin regulates somatostatin receptor subtype mRNA expression in GH3 cells. Bruno, J.F., Xu, Y., Berelowitz, M. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  29. Intraislet somatostatin inhibits insulin (via a subtype-2 somatostatin receptor) but not islet amyloid polypeptide secretion in the isolated perfused human pancreas. Atiya, A.W., Moldovan, S., Adrian, T.E., Coy, D., Walsh, J., Brunicardi, F.C. J. Gastrointest. Surg. (1997) [Pubmed]
  30. Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes. Jaquet, P., Saveanu, A., Gunz, G., Fina, F., Zamora, A.J., Grino, M., Culler, M.D., Moreau, J.P., Enjalbert, A., Ouafik, L.H. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  31. Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1--5 and correlation with receptor protein expression and tumor pathology. Kumar, U., Grigorakis, S.I., Watt, H.L., Sasi, R., Snell, L., Watson, P., Chaudhari, S. Breast Cancer Res. Treat. (2005) [Pubmed]
  32. Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression. Corbetta, S., Ballaré, E., Mantovani, G., Lania, A., Losa, M., Di Blasio, A.M., Spada, A. Eur. J. Clin. Invest. (2001) [Pubmed]
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