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

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 (pD(2)s for CGRP, amylin and adrenomedullin of 7.90+/-0.11, 7.70+/-0.19 and 7.25+/-0.10 respectively). 3 CGRP(8-37) (1 mu M) and AC187 (10 mu M) showed little antagonist activity against adrenomedullin. 4 Adrenomedullin(22-52) by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin. 5 [I-125]-adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC(50) 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 [I-125]-CGRP (pIC(50) = 8.73, capacity = 114 fmol mg(-1), selectivity CGRP > amylin = AC187 > adrenomedullin). [I-125]-amylin bound to two sites with a total capacity of 882 fmol mg(-1). 6 Although CGRP has been shown to act at a CGRP(2) receptor on the vas deferens with low sensitivity to CGRP(8-37), this antagonist displaced [I-125]-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 CGRP(8-37) is not due to temperature differences between binding and functional assays.