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. 1995 Jul;115(6):975–980. doi: 10.1111/j.1476-5381.1995.tb15906.x

Further evidence from functional studies for somatostatin receptor heterogeneity in guinea-pig isolated ileum, vas deferens and right atrium.

W Feniuk 1, J Dimech 1, E M Jarvie 1, P P Humphrey 1
PMCID: PMC1909024  PMID: 7582529

Abstract

1. Somatostatin (SRIF) causes a concentration-dependent inhibition of neurotransmission in guinea-pig ileum and vas deferens as well as negative inotropy in guinea-pig isolated right atrium. The SRIF receptors mediating these effects have now been further characterized by use of the peptides BIM-23027, BIM-23056 and L-362855, reported as selective for the recombinant SRIF receptor types, sst2, sst3 and sst5, respectively. 2. BIM-23027 was a highly potent agonist at causing an inhibition of neurotransmission in the guinea-pig ileum (EC50 value 1.9 nM), being about 3 times more potent than SRIF (EC50 value 6.8 nM). In contrast, in both guinea-pig vas deferens and right atrial preparations, BIM-23027 was a relatively weak agonist being at least 30-100 times weaker than SRIF. In guinea-pig atria, BIM-23027 (3 microM) antagonized the negative inotropic action of SRIF28 (apparent pKB = 5.9 +/- 0.1) but had no effect on the negative inotropic action of cyclohexyladenosine. 3. The inhibitory effect of BIM-23027 in the guinea-pig ileum was readily desensitized. Prior exposure to BIM-23027 (0.3 microM) markedly attenuated the inhibitory effect of SRIF but had no effect on the inhibitory action of clonidine suggesting that BIM-23027 and SRIF act via a common receptor mechanism. 4. L-362855 caused a concentration-dependent inhibition of neurotransmission in both the guinea-pig ileum and vas deferens as well as causing negative inotropy in the guinea-pig atrium but was at least 30-100 times weaker than SRIF. In guinea-pig isolated atria, L-362855 (3 microM) did not antagonize the negative inotropic action of SRIF28.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Amherdt M., Patel Y. C., Orci L. Selective binding of somatostatin-14 and somatostatin-28 to islet cells revealed by quantitative electron microscopic autoradiography. J Clin Invest. 1987 Nov;80(5):1455–1458. doi: 10.1172/JCI113225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bruno J. F., Xu Y., Song J., Berelowitz M. Molecular cloning and functional expression of a brain-specific somatostatin receptor. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11151–11155. doi: 10.1073/pnas.89.23.11151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dimech J., Feniuk W., Humphrey P. P. Antagonist effects of seglitide (MK 678) at somatostatin receptors in guinea-pig isolated right atria. Br J Pharmacol. 1993 Aug;109(4):898–899. doi: 10.1111/j.1476-5381.1993.tb13703.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Feniuk W., Dimech J., Humphrey P. P. Characterization of somatostatin receptors in guinea-pig isolated ileum, vas deferens and right atrium. Br J Pharmacol. 1993 Nov;110(3):1156–1164. doi: 10.1111/j.1476-5381.1993.tb13935.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feniuk W., Humphrey P. P. Somatostatin-induced inhibition of neurotransmission in the mouse isolated vas deferens is resistant to pertussis toxin. Eur J Pharmacol. 1994 Aug 22;261(3):333–337. doi: 10.1016/0014-2999(94)90126-0. [DOI] [PubMed] [Google Scholar]
  6. Hoyer D., Bell G. I., Berelowitz M., Epelbaum J., Feniuk W., Humphrey P. P., O'Carroll A. M., Patel Y. C., Schonbrunn A., Taylor J. E. Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci. 1995 Mar;16(3):86–88. doi: 10.1016/s0165-6147(00)88988-9. [DOI] [PubMed] [Google Scholar]
  7. Kurokawa M., Kirk I. P., Kirkpatrick K. A., Kase H., Richardson P. J. Inhibition by KF17837 of adenosine A2A receptor-mediated modulation of striatal GABA and ACh release. Br J Pharmacol. 1994 Sep;113(1):43–48. doi: 10.1111/j.1476-5381.1994.tb16171.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Mandarino L., Stenner D., Blanchard W., Nissen S., Gerich J., Ling N., Brazeau P., Bohlen P., Esch F., Guillemin R. Selective effects of somatostatin-14, -25 and -28 on in vitro insulin and glucagon secretion. Nature. 1981 May 7;291(5810):76–77. doi: 10.1038/291076a0. [DOI] [PubMed] [Google Scholar]
  9. McKeen E. S., Feniuk W., Humphrey P. P. Mediation by SRIF1 receptors of the contractile action of somatostatin in rat isolated distal colon; studies using some novel SRIF analogues. Br J Pharmacol. 1994 Oct;113(2):628–634. doi: 10.1111/j.1476-5381.1994.tb17036.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. O'Carroll A. M., Lolait S. J., König M., Mahan L. C. Molecular cloning and expression of a pituitary somatostatin receptor with preferential affinity for somatostatin-28. Mol Pharmacol. 1992 Dec;42(6):939–946. [PubMed] [Google Scholar]
  11. O'Carroll A. M., Raynor K., Lolait S. J., Reisine T. Characterization of cloned human somatostatin receptor SSTR5. Mol Pharmacol. 1994 Aug;46(2):291–298. [PubMed] [Google Scholar]
  12. Patel Y. C., Panetta R., Escher E., Greenwood M., Srikant C. B. Expression of multiple somatostatin receptor genes in AtT-20 cells. Evidence for a novel somatostatin-28 selective receptor subtype. J Biol Chem. 1994 Jan 14;269(2):1506–1509. [PubMed] [Google Scholar]
  13. Patel Y. C., Srikant C. B. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5). Endocrinology. 1994 Dec;135(6):2814–2817. doi: 10.1210/endo.135.6.7988476. [DOI] [PubMed] [Google Scholar]
  14. Raynor K., Murphy W. A., Coy D. H., Taylor J. E., Moreau J. P., Yasuda K., Bell G. I., Reisine T. Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides. Mol Pharmacol. 1993 Jun;43(6):838–844. [PubMed] [Google Scholar]
  15. Reisine T., Kong H., Raynor K., Yano H., Takeda J., Yasuda K., Bell G. I. Splice variant of the somatostatin receptor 2 subtype, somatostatin receptor 2B, couples to adenylyl cyclase. Mol Pharmacol. 1993 Nov;44(5):1016–1020. [PubMed] [Google Scholar]
  16. Rens-Domiano S., Law S. F., Yamada Y., Seino S., Bell G. I., Reisine T. Pharmacological properties of two cloned somatostatin receptors. Mol Pharmacol. 1992 Jul;42(1):28–34. [PubMed] [Google Scholar]
  17. Rossowski W. J., Coy D. H. Potent inhibitory effects of a type four receptor-selective somatostatin analog on rat insulin release. Biochem Biophys Res Commun. 1993 Dec 15;197(2):366–371. doi: 10.1006/bbrc.1993.2488. [DOI] [PubMed] [Google Scholar]
  18. Vanetti M., Kouba M., Wang X., Vogt G., Höllt V. Cloning and expression of a novel mouse somatostatin receptor (SSTR2B). FEBS Lett. 1992 Oct 26;311(3):290–294. doi: 10.1016/0014-5793(92)81122-3. [DOI] [PubMed] [Google Scholar]

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