Effect of substance P on mucus secretion of isolated submucosal gland from feline trachea.

To elucidate how substance P (SP) produces submucosal gland secretion, we examined the effects of SP on the glandular contractile response and 3H-labeled glycoconjugate release in isolated submucosal glands from feline tracheae. SP (10(-12) to 10(-4) M) produced dose-dependent increases in the contractile response, and the maximal tension induced by SP was approximately 70% of the response to methacholine. SP-induced contraction is blocked completely by atropine and augmented by neostigmine. Pretreatment with hemicholinium 3, an acetylcholine synthesis inhibitor, inhibited the contractile response to SP. Pretreatment with tetrodotoxin did not inhibit the contractile response to SP. Capsaicin induced tension of a magnitude similar to that of SP. SP (10(-7) M) produced a significant increase (74% above control) in radiolabeled glycoconjugate release from isolated glands, whereas SP had no significant effects on glycoconjugate release from tracheal explants, probably because of epithelial suppression. Atropine abolished SP-evoked glycoconjugate release in isolated glands. Our findings indicate that 1) SP induces glandular contraction, which is related to the squeezing of mucus in the ducts and secretory tubules, 2) SP stimulates radiolabeled glycoconjugate release in isolated submucosal gland, probably involving mucus synthesis and/or cellular secretion, and 3) these two actions are mediated by a peripheral cholinergic mechanism.