Cholinergic and VIP-ergic pathways mediate histamine H2 receptor-induced cyclical secretion in the guinea pig colon.
Previous studies demonstrated neurally mediated recurrent increases in short-circuit current (Isc) 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 H2 receptor agonist, dimaprit, caused cyclical increases in Isc, 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 Isc, which were significantly decreased by mecamylamine, a nicotinic receptor antagonist, and nearly abolished by the muscarinic antagonist, atropine (M3 > M1 = M2). The muscarinic antagonist, 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP, M3 > M1), was more potent than pirenzepine (M1 > M3) in reducing recurrent increases in Isc. Dimaprit- and electrically evoked secretion were inhibited by the VIP antagonists [4Cl-D-Phe6, Leu17]VIP and VIP hybrid. The results suggest the involvement of VIP-ergic and cholinergic neurons utilizing nicotinic and muscarinic synapses in mediating secretion.
Cooke
H J
HJ
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210.
Wang
Y Z
YZ
Reddix
R
R
Javed
N
N
D000109:Acetylcholine / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002794:Choline / Q000502:physiology*; D003106:Colon / Q000378:metabolism*; D017259:Dimaprit / Q000494:pharmacology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006636:Histamine Release; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D010880:Piperidines; D011970:Receptors, Histamine H2; D062367:ortho-Aminobenzoates; D014660:Vasoactive Intestinal Peptide; D010890:Pirenzepine; D001285:Atropine; D000584:Amiloride; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C001209:fenamic acid; D002794:Choline; D000109:Acetylcholine; D017259:Dimaprit