title: Characterisation of calcitonin gene-related peptide receptors in rat atrium and vas deferens: evidence for a [Cys(Et)(2, 7)]hCGRP-preferring receptor.
abstract: The present study was performed in order to characterise calcitonin gene-related 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]carbonyl]pentyl ]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1, 4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-Piperidinecarboxamide (BIBN4096BS), a novel CGRP receptor antagonist. When CGRP was used as an agonist, BIBN4096BS exhibited an almost 10-fold higher affinity for CGRP receptors in rat left atrium compared to those in the vas deferens, indicating that CGRP acts through different CGRP receptor subtypes in these two tissues. In addition, BIBN4096BS was almost 10-fold more potent in antagonizing [Cys(Et)(2,7)]hCGRPalpha and human adrenomedullin-induced responses than CGRP-induced responses 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 subtypes. Namely, the CGRP(2) receptor and a "novel" receptor that possesses low efficacy 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.
authors.affiliation: Biological and Chemical Research, Boehringer Ingelheim Pharma KG, 88397, Biberach, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Eberlein
authors.forename: K
authors.initials: K
authors.lastname: Rudolf
authors.forename: W
authors.initials: W
authors.lastname: Engel
authors.forename: G
authors.initials: G
authors.lastname: Hallermayer
authors.forename: H
authors.initials: H
authors.lastname: Doods
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002316:Cardiotonic Agents / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000819:agonists / Q000378:metabolism*; D015244:Thiorphan / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002316:Cardiotonic Agents; D010446:Peptide Fragments; D010879:Piperazines; D011480:Protease Inhibitors; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D015244:Thiorphan; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant