Luminal addition of tachykinins to the open-circuited canine tracheal epithelium produces a biphasic response in the transmucosal potential difference (PD). A rapid, transient decrease is followed by a subsequent rise, both phases being associated with changes in conductance. Concentration-response curves demonstrated the following orders of potency: substance P greater than physalaemin greater than eledoisin = kassinin for the tachykinins, and substance P greater than substance P-(4-11) greater than substance P-(6-11) using the C-terminal fragments. Both sequences are similar to those reported for the dog carotid artery. These observations were confirmed by cross-tachyphylaxis experiments. SP-O-methyl ester, a selective agonist for the SP-P (or NK-1) receptor, elicited identical responses, and exhibited cross-tachyphylaxis to substance P. Bradykinin produced similar luminal responses, though different receptors are involved, since no cross-tachyphylaxis was observed between bradykinin and the tachykinins.
