Characterization of receptors for calcitonin gene-related peptide and adrenomedullin on the guinea-pig vas deferens

Br J Pharmacol. 1999 Mar;126(5):1276-82. doi: 10.1038/sj.bjp.0702437.


1. The receptors which mediate the effects of calcitonin gene-related peptide (CGRP), amylin and adrenomedullin on the guinea-pig vas deferens have been investigated. 2. All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD2s for CGRP, amylin and adrenomedullin of 7.90+/-0.11, 7.70+/-0.19 and 7.25+/-0.10 respectively). 3. CGRP8-37 (1 microM) and AC187 (10 microM) showed little antagonist activity against adrenomedullin. 4. Adrenomedullin22-52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin. 5. [125I]-adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC50 of 8.91 and a capacity of 643 fmol mg(-1). Its selectivity profile was adrenomedullin> AC187>CGRP=amylin. It was clearly distinct from a site labelled by [125I]-CGRP (pIC50=8.73, capacity=114 fmol mg(-1), selectivity CGRP>amylin=AC187>adrenomedullin). [125I]-amylin bound to two sites with a total capacity of 882 fmol mg(-1). 6. Although CGRP has been shown to act at a CGRP2 receptor on the vas deferens with low sensitivity to CGRP8-37, this antagonist displaced [125I]-CGRP with high affinity from vas deferens membranes. This affinity was unaltered by increasing the temperature from 4 degrees C to 25 degrees C, suggesting the anomalous behaviour of CGRP8-37 is not due to temperature differences between binding and functional assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin
  • Amyloid / pharmacology
  • Animals
  • Binding, Competitive
  • Calcitonin Gene-Related Peptide / pharmacology
  • Guinea Pigs
  • Iodine Radioisotopes
  • Islet Amyloid Polypeptide
  • Male
  • Membrane Proteins / metabolism*
  • Muscle Contraction / drug effects
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology
  • Radioligand Assay
  • Receptors, Adrenomedullin
  • Receptors, Calcitonin Gene-Related Peptide / metabolism*
  • Receptors, Peptide*
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism*
  • Vasodilator Agents / pharmacology


  • Amyloid
  • Iodine Radioisotopes
  • Islet Amyloid Polypeptide
  • Membrane Proteins
  • Peptide Fragments
  • Peptides
  • Receptors, Adrenomedullin
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, Peptide
  • Vasodilator Agents
  • calcitonin gene-related peptide (8-37)
  • Adrenomedullin
  • Calcitonin Gene-Related Peptide