Tachykinin-induced anion secretion in guinea pig distal colon: role of neural and inflammatory mediators.

The effects of substance P and related tachykinins on short-circuit current were determined in submucosa-mucosa sheets of guinea pig distal colon. Substance P, neurokinin A, eledoisin and physalaemin evoked a concentration-dependent increase in short-circuit current with a rank order of potencies of substance P = physalaemin greater than eledoisin = neurokinin A. The substance P response was reduced in chloride-free solutions or after addition of furosemide. Tetrodotoxin, atropine, mecamylamine and pyrilamine reduced the response to substance P. The substance P antagonist, [D-Arg1,D-Phe5,Trp7,9,Leu11]-substance P, reduced the response to neural stimulation and to exogenous substance P. The results suggest that substance P evokes anion secretion by activating cholinergic and noncholinergic neurons and by releasing histamine.