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Am J Physiol Gastrointest Liver Physiol 275: G76-G84, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 1, G76-G84, July 1998

Histamine stimulates ion transport by dog pancreatic duct epithelial cells through H1 receptors

Toan D. Nguyen, Charles N. Okolo, and Mark W. Moody

Department of Medicine, University of Washington, and Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108

Histamine affects pancreatic secretion, but its direct action on ion transport by pancreatic duct epithelial cells (PDEC) has not been defined. We now characterize the secretory effects of histamine on cultured, well-differentiated, and nontransformed dog PDEC. Histamine stimulated, in a concentration-dependent manner (1-100 µM), a cellular 125I- efflux that was inhibited by 500 µM 5-nitro-2-(3-phenylpropylamino)benzoic acid, 2.5 mM diphenylamine-2-carboxylate, and 500 µM DIDS and thus mediated through Ca2+-activated Cl- channels. Histamine-stimulated 125I- efflux was 1) inhibited by 100 µM diphenhydramine, an H1 receptor antagonist, 2) resistant to 1 mM cimetidine, an H2 receptor antagonist, 3) not reproduced by 1 mM dimaprit, an H2 agonist, and 4) inhibited by 50 µM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a Ca2+ chelator, suggesting that it was mediated through H1 receptors acting via increased cytosolic Ca2+. Histamine also stimulated a 86Rb+ efflux that was sensitive to 100 nM charybdotoxin and thus mediated through Ca2+-activated K+ channels. When PDEC monolayers were studied in Ussing chambers, a short-circuit current of 21.7 ± 3.1 µA/cm2 was stimulated by 100 µM histamine. This effect was inhibited by diphenhydramine but not cimetidine, was not reproduced with dimaprit, and was observed only after serosal addition of histamine, suggesting that it was mediated by basolateral H1 receptors on PDEC. In conclusion, histamine, acting through basolateral H1 receptors, activates both Ca2+-activated Cl- and K+ channels; in this manner, it may regulate PDEC secretion in normal or inflamed pancreas.

chloride channels; potassium channels; Ussing chamber


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