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. 1996 Mar;117(6):1362–1368. doi: 10.1111/j.1476-5381.1996.tb16737.x

Multiple receptors for calcitonin gene-related peptide and amylin on guinea-pig ileum and vas deferens.

A E Tomlinson 1, D R Poyner 1
PMCID: PMC1909800  PMID: 8882637

Abstract

1. The responses of the electrically stimulated guinea-pig ileum and vas deferens to human and rat calcitonin gene-related peptide (CGRP) and amylin were investigated. 2. The inhibition of contraction of the ileum produced by human alpha CGRP was antagonized by human alpha CGRP8-37 (apparent pA2 estimated at 7.15 +/- 0.23) > human alpha CGRP19-37 (apparent pA2 estimated as 6.67 +/- 0.33) > [Tyr0]-human alpha CGRP28-37. The amylin antagonist, AC187, was three fold less potent than CGRP8-37 in antagonizing human alpha CGRP. 3. Both human beta- and rat alpha CGRP inhibited contractions of the ileum, but this was less sensitive to inhibition by CGRP8-37 than the effect of human alpha CGRP. However, CGRP19-37 was twenty times more effective in inhibiting the response to rat alpha CGRP (apparent pA2 estimated as 8.0 +/- 0.1) compared to human alpha CGRP. 4. Rat amylin inhibited contractions in about 10% of ileal preparations; this effect was not antagonized by any CGRP fragment. Human amylin had no action on this preparation. 5. Both human and rat alpha CGRP inhibited electrically stimulated contractions of the vas deferens, which were not antagonized by 3 microM CGRP8-37 or 10 microM AC187. 6. Rat amylin inhibited the stimulated contractions of the vas deferens (EC50 = 77 +/- 9 nM); human amylin was less potent (EC50 = 213 +/- 22 nM). The response to rat amylin was antagonized by 10 microM CGRP8-37 (EC50 = 242 +/- 25 nM) and 10 microM AC187 (EC50 = 610 +/- 22 nM). 7. It is concluded that human alpha CGRP relaxes the guinea-pig ileum via CGRP1-like receptors, but that human beta CGRP and rat alpha CGRP may use additional receptors. These are distinct CGRP2-like and amylin receptors on guinea-pig vas deferens.

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Selected References

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  1. Beaumont K., Kenney M. A., Young A. A., Rink T. J. High affinity amylin binding sites in rat brain. Mol Pharmacol. 1993 Sep;44(3):493–497. [PubMed] [Google Scholar]
  2. Beaumont K., Pittner R. A., Moore C. X., Wolfe-Lopez D., Prickett K. S., Young A. A., Rink T. J. Regulation of muscle glycogen metabolism by CGRP and amylin: CGRP receptors not involved. Br J Pharmacol. 1995 Jul;115(5):713–715. doi: 10.1111/j.1476-5381.1995.tb14991.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhogal R., Sheldrick R. L., Coleman R. A., Smith D. M., Bloom S. R. The effects of IAPP and CGRP on guinea pig tracheal smooth muscle in vitro. Peptides. 1994;15(7):1243–1247. doi: 10.1016/0196-9781(94)90148-1. [DOI] [PubMed] [Google Scholar]
  4. Cassels B. K., Asencio M., Conget P., Speisky H., Videla L. A., Lissi E. A. Structure-antioxidative activity relationships in benzylisoquinoline alkaloids. Pharmacol Res. 1995 Feb;31(2):103–107. doi: 10.1016/1043-6618(95)80054-9. [DOI] [PubMed] [Google Scholar]
  5. Chakder S., Rattan S. [Tyr0]-calcitonin gene-related peptide 28-37 (rat) as a putative antagonist of calcitonin gene-related peptide responses on opossum internal anal sphincter smooth muscle. J Pharmacol Exp Ther. 1990 Apr;253(1):200–206. [PubMed] [Google Scholar]
  6. Chantry A., Leighton B., Day A. J. Cross-reactivity of amylin with calcitonin-gene-related peptide binding sites in rat liver and skeletal muscle membranes. Biochem J. 1991 Jul 1;277(Pt 1):139–143. doi: 10.1042/bj2770139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deems R. O., Cardinaux F., Deacon R. W., Young D. A. Amylin or CGRP (8-37) fragments reverse amylin-induced inhibition of 14C-glycogen accumulation. Biochem Biophys Res Commun. 1991 Nov 27;181(1):116–120. doi: 10.1016/s0006-291x(05)81389-0. [DOI] [PubMed] [Google Scholar]
  8. Dennis T., Fournier A., Cadieux A., Pomerleau F., Jolicoeur F. B., St Pierre S., Quirion R. hCGRP8-37, a calcitonin gene-related peptide antagonist revealing calcitonin gene-related peptide receptor heterogeneity in brain and periphery. J Pharmacol Exp Ther. 1990 Jul;254(1):123–128. [PubMed] [Google Scholar]
  9. Dennis T., Fournier A., St Pierre S., Quirion R. Structure-activity profile of calcitonin gene-related peptide in peripheral and brain tissues. Evidence for receptor multiplicity. J Pharmacol Exp Ther. 1989 Nov;251(2):718–725. [PubMed] [Google Scholar]
  10. Ellis J. L., Burnstock G. Modulation of neurotransmission in the guinea-pig vas deferens by capsaicin: involvement of calcitonin gene-related peptide and substance P. Br J Pharmacol. 1989 Oct;98(2):707–713. doi: 10.1111/j.1476-5381.1989.tb12646.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Giuliani S., Wimalawansa S. J., Maggi C. A. Involvement of multiple receptors in the biological effects of calcitonin gene-related peptide and amylin in rat and guinea-pig preparations. Br J Pharmacol. 1992 Oct;107(2):510–514. doi: 10.1111/j.1476-5381.1992.tb12775.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hughes S. R., Brain S. D. A calcitonin gene-related peptide (CGRP) antagonist (CGRP8-37) inhibits microvascular responses induced by CGRP and capsaicin in skin. Br J Pharmacol. 1991 Nov;104(3):738–742. doi: 10.1111/j.1476-5381.1991.tb12497.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jansen I. Characterization of calcitonin gene-related peptide (CGRP) receptors in guinea pig basilar artery. Neuropeptides. 1992 Feb;21(2):73–79. doi: 10.1016/0143-4179(92)90517-z. [DOI] [PubMed] [Google Scholar]
  14. Kerr D. I., Ong J., Prager R. H. Antagonism of GABAB-receptor-mediated responses in the guinea-pig isolated ileum and vas deferens by phosphono-analogues of GABA. Br J Pharmacol. 1990 Feb;99(2):422–426. doi: 10.1111/j.1476-5381.1990.tb14719.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Longmore J., Hogg J. E., Hutson P. H., Hill R. G. Effects of two truncated forms of human calcitonin-gene related peptide: implications for receptor classification. Eur J Pharmacol. 1994 Nov 14;265(1-2):53–59. doi: 10.1016/0014-2999(94)90222-4. [DOI] [PubMed] [Google Scholar]
  16. Maggi C. A., Chiba T., Giuliani S. Human alpha-calcitonin gene-related peptide-(8-37) as an antagonist of exogenous and endogenous calcitonin gene-related peptide. Eur J Pharmacol. 1991 Jan 3;192(1):85–88. doi: 10.1016/0014-2999(91)90072-x. [DOI] [PubMed] [Google Scholar]
  17. Mimeault M., Fournier A., Dumont Y., St-Pierre S., Quirion R. Comparative affinities and antagonistic potencies of various human calcitonin gene-related peptide fragments on calcitonin gene-related peptide receptors in brain and periphery. J Pharmacol Exp Ther. 1991 Sep;258(3):1084–1090. [PubMed] [Google Scholar]
  18. Nuki C., Kawasaki H., Takasaki K., Wada A. Pharmacological characterization of presynaptic calcitonin gene-related peptide (CGRP) receptors on CGRP-containing vasodilator nerves in rat mesenteric resistance vessels. J Pharmacol Exp Ther. 1994 Jan;268(1):59–64. [PubMed] [Google Scholar]
  19. Poyner D. R., Andrew D. P., Brown D., Bose C., Hanley M. R. Pharmacological characterization of a receptor for calcitonin gene-related peptide on rat, L6 myocytes. Br J Pharmacol. 1992 Feb;105(2):441–447. doi: 10.1111/j.1476-5381.1992.tb14272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Poyner D. R. Calcitonin gene-related peptide: multiple actions, multiple receptors. Pharmacol Ther. 1992;56(1):23–51. doi: 10.1016/0163-7258(92)90036-y. [DOI] [PubMed] [Google Scholar]
  21. Rink T. J., Beaumont K., Koda J., Young A. Structure and biology of amylin. Trends Pharmacol Sci. 1993 Apr;14(4):113–118. doi: 10.1016/0165-6147(93)90081-t. [DOI] [PubMed] [Google Scholar]
  22. Rovero P., Giuliani S., Maggi C. A. CGRP antagonist activity of short C-terminal fragments of human alpha CGRP, CGRP(23-37) and CGRP(19-37). Peptides. 1992 Sep-Oct;13(5):1025–1027. doi: 10.1016/0196-9781(92)90067-d. [DOI] [PubMed] [Google Scholar]
  23. Sun Y. D., Benishin C. G. Effects of calcitonin gene-related peptide on longitudinal muscle and myenteric plexus of guinea pig ileum. J Pharmacol Exp Ther. 1991 Dec;259(3):947–952. [PubMed] [Google Scholar]
  24. Young A. A., Gedulin B., Gaeta L. S., Prickett K. S., Beaumont K., Larson E., Rink T. J. Selective amylin antagonist suppresses rise in plasma lactate after intravenous glucose in the rat. Evidence for a metabolic role of endogenous amylin. FEBS Lett. 1994 May 2;343(3):237–241. doi: 10.1016/0014-5793(94)80563-6. [DOI] [PubMed] [Google Scholar]

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