Carbamylcholine- and 5-hydroxytryptamine-induced contraction in rat isolated airways: inhibition by calcitonin gene-related peptide.

1. The effects of rat and human alpha-calcitonin gene-related peptide (alpha-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 x 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.