SUBSTANCE-P STIMULATION OF CHLORIDE SECRETION BY CANINE TRACHEAL MUCOSA

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Abstract
The effect of a neuropeptide, substance P, on the electrical and ion transport properties of dog trachea were investigated. Posterior mucosal tissues were mounted in Ussing chambers and bathed with Krebs-Henseleit solution, pH 7.4, at 37.degree. C. The solution was gassed with 95% O2, 5% CO2. Substance P (10-7 M) added to the mucosal bath elicited within seconds a rapid rise in short circuit current with a peak response of 23 .mu.A .cntdot. cm-2 and an increase in tissue conductance of 0.63 mS .cntdot. cm-2 (P < 0.001, n = 20). In 6 experiments, 36Cl and 22Na fluxes were measured under short circuit conditions and they revealed that net Cl secretion increased from 1.46 .+-. 0.41 to 2.30 .+-. 0.74 .mu.eq .cntdot. cm-2.cntdot.h-1 (mean .+-. SE, P < 0.05). This increase was brought about by enhancement of unidirectional submucosa to lumen flux. Net Na absorption of 0.63 .+-. 0.09 did not change significantly (0.49 .+-. 0.16). Short circuit current responses to substance P was not modified by prior tissue incubation with atropine, phenoxybenzamine, propranolol or naloxone. Removal of mucosal bath Ca and the presence of Ca channel blocker verapamil did not abolish tissue response to substance P. Nerve fibers containing substance P may play a role in regulation of ion transport across the trachea. This action does not appear to be related to the cholinergic, adrenergic or opiate receptors.