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Carbamylcholine‐ and 5‐hydroxytryptamine‐induced contraction in rat isolated airways: inhibition by calcitonin gene‐related peptide
Author(s) -
Cadieux Alain,
Lanoue Chantal,
Sirois Pierre,
Barabe Jean
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12112.x
Subject(s) - calcitonin gene related peptide , medicine , endocrinology , bronchus , contraction (grammar) , calcitonin , parenchyma , inhibitory postsynaptic potential , chemistry , propranolol , tetrodotoxin , muscle contraction , neuropeptide , biology , lung , receptor , pathology , respiratory disease
1 The effects of rat and human α‐calcitonin gene‐related peptide (α‐CGRP) were investigated in isolated smooth muscle preparations obtained from three levels of the rat respiratory tract. 2 Neither peptide (10 −10 –10 −6 m ) had any effect on resting tension or on carbamylcholine (10 −6 m )‐induced tone of trachea or main bronchus. In contrast, CGRP sometimes reduced spontaneous or carbamylcholine‐induced tone of lung parenchymal strips. 3 CGRP produced a significant rightward shift of the log concentration‐response curves to carbamylcholine and 5‐hydroxytryptamine (5‐HT) in the main bronchus. A rightward shift was also seen in trachea and parenchymal strips but this did not achieve the level of significance. The maximal response to 5‐HT was reduced in the main bronchus and lung parenchyma whereas the maximal contraction to carbamylcholine was decreased in parenchymal strip only. 4 In all three airway preparations, CGRP caused concentration‐dependent inhibition of responses elicited by challenges with 10 −7 m carbamylcholine or 5 × 10 −7 m 5‐HT. The inhibitory effect of the peptide was inversely related to the size of the airways: the smaller the calibre, the greater the inhibition. 5 The inhibitory action of CGRP was not modified by pretreatment with tetrodotoxin (10 −6 m ), propranolol (10 −6 m ) or indomethacin (10 −6 m ). 6 The results strongly suggest that (a) CGRP has a nonspecific inhibitory action on airway smooth muscle cells, (b) CGRP may act as a potent inhibitor of responses elicited by bronchoconstrictor substances and (c) its inhibitory activity may be most powerfully expressed in peripheral regions of the respiratory tract.