Cholinergic and VIP-ergic pathways mediate histamine H2 receptor-induced cyclical secretion in the guinea pig colon
Cooke, H.J.; Wang, Y.Z.; Reddix, R.; Javed, N.
American Journal of Physiology 268(3 Pt 1): G465-G470
1995
ISSN/ISBN: 0002-9513 PMID: 7534994 Document Number: 449224
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 muscle-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-phenylanthranilic acid, but not by the sodium channel blocker amiloride. Dimaprit stimulated release of (3H)acetylcholine and vasoactive intestinal polypeptide (VIP) from submucosal/mucosal sheets. Dimaprit caused recurrent increases in I-sc, which were significantly decreased by mecamylamine, a nicotinic receptor antagonist, and nearly abolished by the muscarinic antagonist, atropine (M-3 gt M-1 = M-2). The muscarinic antagonist, 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP, M-3 gt M-1), was more potent than pirenzepine (M-1 gt M-3) in reducing recurrent increases in I-sc. Dimaprit- and electrically evoked secretion were inhibited by the VIP antagonists (4C)-D-Phe-6, Leu-17)IP and VIP hybrid. The results suggest the involvement of VIP-ergic and cholinergic neurons utilizing nicotinic and muscarinic synapses in mediating secretion.