Dm. Wu et al., Characterisation of calcitonin gene-related peptide receptors in rat atrium and vas deferens: evidence for a [Cys(Et)(2,7)]hCGRP-preferring receptor, EUR J PHARM, 400(2-3), 2000, pp. 313-319
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.
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