Effects of two truncated forms of human calcitonin-gene related peptide: implications for receptor classification

Eur J Pharmacol. 1994 Nov 14;265(1-2):53-9. doi: 10.1016/0014-2999(94)90222-4.

Abstract

We investigated the possibility that human alpha-calcitonin-gene related peptide (CGRP)-(8-37) and human beta CGRP-(8-37) show some selectivity as antagonists of CGRP1 and CGRP2 receptor-mediated responses. Bindings assays showed that human alpha CGRP, human alpha CGRP-(8-37) and human beta CGRP-(8-37) showed high affinity (in the nanomolar concentration range) for CGRP receptors expressed in SK-N-MC cells and also in rat brain membrane preparations. Both human alpha CGRP-(8-37) and human beta CGRP-(8-37) were potent antagonists of human alpha CGRP-stimulated cAMP accumulation in SK-N-MC cells. However, both human alpha CGRP-(8-37) and human beta CGRP-(8-37) were weakly effective in antagonizing human alpha CGRP-stimulated responses in guinea-pig atria and rat vas deferens. In rat vas deferens, but not guinea-pig atria, the effects of human alpha CGRP and human alpha CGRP-(8-37) (but not human beta CGRP-(8-37)) were potentiated by thiorphan. Neither human alpha- nor human beta CGRP-(8-37) showed selectivity for supposedly CGRP1 and CGRP2 receptor-mediated responses. Furthermore, differences in the effects of the truncated CGRP analogues may reflect differences in enzyme distribution rather than the existence of CGRP receptor subtypes.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Brain / metabolism*
  • Calcitonin Gene-Related Peptide / antagonists & inhibitors*
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Cell Line
  • Cyclic AMP / pharmacology
  • Guinea Pigs
  • Heart Atria / drug effects
  • Humans
  • Iodine Isotopes
  • Male
  • Neurons / metabolism*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcitonin Gene-Related Peptide / classification*
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • Thiorphan / pharmacology
  • Vas Deferens / drug effects

Substances

  • Iodine Isotopes
  • Peptide Fragments
  • Receptors, Calcitonin Gene-Related Peptide
  • calcitonin gene-related peptide (8-37)
  • Thiorphan
  • Cyclic AMP
  • Adenylyl Cyclases
  • Calcitonin Gene-Related Peptide