CHOLINERGIC AND VIP-ERGIC PATHWAYS MEDIATE HISTAMINE H-2 RECEPTOR-INDUCED CYCLICAL SECRETION IN THE GUINEA-PIG COLON

Previous studies demonstrated neurally mediated recurrent increases in short-circuit current (I-sc) suggestive of anion secretion in guinea pig distal colon. To determine the neural pathways involved, segments of distal colon from guinea pigs were mounted in flux chambers. In mus cle-stripped or whole thickness preparations, serosal addition of the histamine H-2 receptor agonist, dimaprit, caused cyclical increases in I-sc, which were reduced by the chloride channel blocker, N-phenylant hranilic acid, but not by the sodium channel blocker amiloride. Dimapr it stimulated release of [H-3]acetylcholine and vasoactive intestinal polypeptide (VIP) from submucosal/mucosal sheets. Dimaprit caused recu rrent increases in I-sc, which were significantly decreased by mecamyl amine, a nicotinic receptor antagonist, and nearly abolished by the mu scarinic antagonist, atropine (M(3) > M(1) = M(2)). The muscarinic ant agonist, 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP, M(3 ) > M(1)), was more potent than pirenzepine (M(1) > M(3)) in reducing recurrent increases in I-sc. Dimaprit- and electrically evoked secreti on were inhibited by the VIP antagonists [4C1-D-Phe(6), Leu(17)]VIP an d VIP hybrid. The results suggest the involvement of VIP-ergic and cho linergic neurons utilizing nicotinic and muscarinic synapses in mediat ing secretion.