Cholecystokinin-octapeptide constricts guinea-pig and human airways

1. Cholecystokinin-octapeptide (CCK-OP, 10(-10)-3 x 10(-6) M) produced a concentration-dependent contractile response in guinea-pig trachea which was enhanced by both the mechanical removal of the epithelium and by indomethacin (10(-5) M), with an EC50 of 6.18 +/- 0.10 x 10(-8) M. 2. Sub-threshold concentrations of CCK-OP, which did not alter the resting tone of the smooth muscle, did not alter responses produced to electrical field stimulation (EFS) or to vagal nerve stimulation in an intact tracheal tube preparation. Atropine (2 x 10(-6) M) did not alter the concentration-response curve to CCK-OP, indicating that CCK-OP contraction is not mediated by cholinergic mechanisms. 3. The inhibition of neutral endopeptidase (endopeptidase-24.11) by phosphoramidon (10(-5) M) gave a leftward shift in the CCK-OP concentration-response curve in tissues with intact epithelium obtained from normal animals, but had no effect in tissues denuded of epithelium or in tissues obtained from animals which had been actively sensitized and challenged with ovalbumin (OA). 4. CCK-OP-induced contractile responses were antagonized by the CCK-receptor antagonists dibutyryl cyclic guanosine monophosphate (pA2 = 4.3) and L-364,718 (pA2 = 9.6). 5. CCK-OP induced bronchoconstriction in large, but not small, human airways and was antagonized by the CCK-receptor antagonist L-364,718. CCK-OP had no effect on cholinergic neural responses elicited by EFS in human airways.