Characterisation of calcitonin gene-related peptide receptors in rat atrium and vas deferens: evidence for a [Cys(Et)(2,7)]hCGRP-preferring receptor

The present study was performed in order to characterise calcitonin gene-re lated peptide (CGRP) receptor subtypes in rat left atrium and vas deferens by using [R-(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbo nyI]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1, 4-dihydro-2-oxo-3(2 H)-quinazolinyl)-,1-Piperidinecarboxamide (BIBN4096BS), a novel CGRP receptor antagonist. When CGRP was used as an agonist, BIBN40 96BS exhibited an almost 10-fold higher affinity for CGRP receptors in rat left atrium compared to those in the vas deferens, indicating that CGRP act s through different CGRP receptor subtypes in these two tissues. In additio n, BIBN4096BS was almost 10-fold more potent in antagonizing [Cys(Et)(2,7)] hCGRP alpha and human adrenomedullin-induced responses than CGRP-induced re sponses in rat vas deferens. This might indicate receptor heterogeneity in rat vas deferens. Accordingly, the present work provides first experimental evidence that the rat vas deferens contains two CGRP-like receptor subtype s. Namely, the CGRP, receptor and a "novel" receptor that possesses low eff icacy for CGRP and that is selectively stimulated by [Cys(Et)(2,7)]hCGRP or adrenomedullin and which can be blocked with high affinity by BIBN4096BS. (C) 2000 Elsevier Science B.V. All rights reserved.