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

摘要

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 αCGRP was antagonized by human αCGRP_(8-37) (apparent pA_2 estimated at 7.15 ± 0.23) > human αCGRP_(19-37) (apparent pA_2 estimated as 6.67 ± 0.33) > [Tyr~0]-human αCGRP_(28_37). The amylin antagonist, AC187, was three fold less potent than CGRP_(8-37) in antagonizing human αCGRP. 3 Both human β- and rat αCGRP inhibited contractions of the ileum, but this was less sensitive to inhibition by CGRP_(8-37) than the effect of human αCGRP. However, CGRP_(19-37) was twenty times more effective in inhibiting the response to rat αCGRP (apparent pA_2 estimated as 8.0 ± 0.1) compared to human αCGRP. 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 αCGRP inhibited electrically stimulated contractions of the vas deferens, which were not antagonized by 3 μM CGRP_(8-37) or 10 μM AC187. 6 Rat amylin inhibited the stimulated contractions of the vas deferens (EC_(50) = 77 ± 9 nM); human amylin was less potent (EC_(50) = 213 ± 22 nM). The response to rat amylin was antagonized by 10 μM CGRP_(8-37) (EC_(50) = 242 ± 25 nM) and 10 μM AC187 (EC_(50) = 610±22 nM). 7 It is concluded that human αCGRP relaxes the guinea-pig ileum via CGRP_1-like receptors, but that human βCGRP and rat αCGRP may use additional receptors. These are distinct CGRP_2-like and amylin receptors on guinea-pig vas deferens.