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Gene Review

SSTR3  -  somatostatin receptor 3

Homo sapiens

Synonyms: SS-3-R, SS3-R, SS3R, SSR-28, Somatostatin receptor type 3
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Disease relevance of SSTR3


High impact information on SSTR3

  • In contrast, SSTR3 uniquely triggers PTP-dependent apoptosis accompanied by activation of p53 and the pro-apoptotic protein Bax [6].
  • 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd, 2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM) [7].
  • Binding of 99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3-octreotide (IC50, 20 nM) [7].
  • Of 55 tumors, 12 expressed SSTR1, and 14 expressed SSTR3 mRNA [8].
  • SSTR3 was detected in occasional alpha-cells, and SSTR4 was absent [9].

Chemical compound and disease context of SSTR3


Biological context of SSTR3

  • We demonstrate that apoptosis is signaled uniquely through human SSTR3 and is associated with dephosphorylation-dependent conformational change in wild-type (wt) p53 as well as induction of Bax [12].
  • Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3 [12].
  • The nucleotide sequences of the SSTR3 and SSTR4 genes in COR-L103 cells were normal [13].
  • Cellular transfection of SSTR3 and measurement of SST-dependent AC activity through co-transfected chimeric G alpha(s) revealed that SSTR3 recognizes the C-termini of G alpha(i1/2) but not of G alpha(o) or G alpha(z), and those of G alpha(14) and G alpha(16), but not of G alpha(q) or G alpha(11) [14].
  • Competitive protein binding method was also used to evaluate the role of SSTR3 [10].

Anatomical context of SSTR3


Associations of SSTR3 with chemical compounds

  • Studies using cells transiently coexpressing the human dopamine D1 receptor and human SSTR3 showed that somatostatin was able to inhibit dopamine-stimulated cAMP formation in a dose-dependent manner, indicating that SSTR3 was functionally coupled to adenylyl cyclase [16].
  • Agonist-dependent internalization of the rat somatostatin receptor subtype 3 (SSTR3) requires four hydroxyl amino acids (Ser341, Ser346, Ser351, and Thr357) in the receptor C terminus (Roth, A., Kreienkamp, H.-J., Nehring, R., Roostermann, D., Meyerhof, W. and Richter, D. (1997) DNA Cell Biol. 16, 111-119) [18].

Physical interactions of SSTR3

  • These findings indicate that the carboxy-terminal third of Gi alpha 1 interacts with SSTR3 and is important in transmitting the signal of SSTR3 activation to adenylyl cyclase [19].

Regulatory relationships of SSTR3

  • SRIF inhibited cAMP formation in cells expressing SSTR3 and the Gi alpha 2/Gi alpha 1 chimera [19].
  • HRECs exposed to the SSTR2 or SSTR3 agonists expressed IGFBP-3 in a concentration-dependent manner [20].
  • In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH [11].

Other interactions of SSTR3


Analytical, diagnostic and therapeutic context of SSTR3


  1. Somatostatin receptor subtype gene expression in pituitary adenomas. Miller, G.M., Alexander, J.M., Bikkal, H.A., Katznelson, L., Zervas, N.T., Klibanski, A. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  2. Somatostatin receptors in pituitary and development of somatostatin receptor subtype-selective analogs. Shimon, I. Endocrine (2003) [Pubmed]
  3. Somatostatin and somatostatin receptors in the diagnosis and treatment of gliomas. Lamszus, K., Meyerhof, W., Westphal, M. J. Neurooncol. (1997) [Pubmed]
  4. Expression of somatostatin receptors in normal and cirrhotic human liver and in hepatocellular carcinoma. Reynaert, H., Rombouts, K., Vandermonde, A., Urbain, D., Kumar, U., Bioulac-Sage, P., Pinzani, M., Rosenbaum, J., Geerts, A. Gut (2004) [Pubmed]
  5. 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]
  6. Somatostatin and its receptor family. Patel, Y.C. Frontiers in neuroendocrinology. (1999) [Pubmed]
  7. Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829. Virgolini, I., Leimer, M., Handmaker, H., Lastoria, S., Bischof, C., Muto, P., Pangerl, T., Gludovacz, D., Peck-Radosavljevic, M., Lister-James, J., Hamilton, G., Kaserer, K., Valent, P., Dean, R. Cancer Res. (1998) [Pubmed]
  8. Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Reubi, J.C., Schaer, J.C., Waser, B., Mengod, G. Cancer Res. (1994) [Pubmed]
  9. Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. Kumar, U., Sasi, R., Suresh, S., Patel, A., Thangaraju, M., Metrakos, P., Patel, S.C., Patel, Y.C. Diabetes (1999) [Pubmed]
  10. The effect of somatostatin and SSTR3 on proliferation and apoptosis of gastric cancer cells. Hu, C., Yi, C., Hao, Z., Cao, S., Li, H., Shao, X., Zhang, J., Qiao, T., Fan, D. Cancer Biol. Ther. (2004) [Pubmed]
  11. G protein coupled receptor signaled apoptosis is associated with activation of a cation insensitive acidic endonuclease and intracellular acidification. Sharma, K., Srikant, C.B. Biochem. Biophys. Res. Commun. (1998) [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. Point mutation of the somatostatin receptor 2 gene in the human small cell lung cancer cell line COR-L103. Zhang, C.Y., Yokogoshi, Y., Yoshimoto, K., Fujinaka, Y., Matsumoto, K., Saito, S. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  14. A novel system that reports the G-proteins linked to a given receptor: a study of type 3 somatostatin receptor. Komatsuzaki, K., Murayama, Y., Giambarella, U., Ogata, E., Seino, S., Nishimoto, I. FEBS Lett. (1997) [Pubmed]
  15. 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]
  16. Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Yamada, Y., Reisine, T., Law, S.F., Ihara, Y., Kubota, A., Kagimoto, S., Seino, M., Seino, Y., Bell, G.I., Seino, S. Mol. Endocrinol. (1992) [Pubmed]
  17. Distribution and second messenger coupling of four somatostatin receptor subtypes expressed in brain. Kaupmann, K., Bruns, C., Hoyer, D., Seuwen, K., Lübbert, H. FEBS Lett. (1993) [Pubmed]
  18. Phosphorylation of four amino acid residues in the carboxyl terminus of the rat somatostatin receptor subtype 3 is crucial for its desensitization and internalization. Roth, A., Kreienkamp, H.J., Meyerhof, W., Richter, D. J. Biol. Chem. (1997) [Pubmed]
  19. Gi alpha 1 selectively couples somatostatin receptor subtype 3 to adenylyl cyclase: identification of the functional domains of this alpha subunit necessary for mediating the inhibition by somatostatin of cAMP formation. Law, S.F., Zaina, S., Sweet, R., Yasuda, K., Bell, G.I., Stadel, J., Reisine, T. Mol. Pharmacol. (1994) [Pubmed]
  20. Expression of IGFBP-3 by human retinal endothelial cell cultures: IGFBP-3 involvement in growth inhibition and apoptosis. Spoerri, P.E., Caballero, S., Wilson, S.H., Shaw, L.C., Grant, M.B. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  21. Expression of somatostatin receptor subtypes (SSTR1-5) in Alzheimer's disease brain: an immunohistochemical analysis. Kumar, U. Neuroscience (2005) [Pubmed]
  22. 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]
  23. Pituitary cell line GH3 expresses two somatostatin receptor subtypes that inhibit adenylyl cyclase: functional expression of rat somatostatin receptor subtypes 1 and 2 in human embryonic kidney 293 cells. Garcia, P.D., Myers, R.M. Mol. Pharmacol. (1994) [Pubmed]
  24. Further delineation of the continuous human neoplastic enterochromaffin cell line, KRJ-I, and the inhibitory effects of lanreotide and rapamycin. Kidd, M., Eick, G.N., Modlin, I.M., Pfragner, R., Champaneria, M.C., Murren, J. J. Mol. Endocrinol. (2007) [Pubmed]
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