HISTAMINE STIMULATES ION-TRANSPORT BY DOG PANCREATIC DUCT EPITHELIAL-CELLS THROUGH H-1 RECEPTORS

Histamine affects pancreatic secretion, but its direct action on ion t ransport by pancreatic duct epithelial cells (PDEC) has not been defin ed. We now characterize the secretory effects of histamine on cultured , well-differentiated, and nontransformed dog PDEC. Histamine stimulat ed, in a concentration-dependent manner (1-100 mu M), a cellular I-125 (-) efflux that was inhibited by 500 mu M 5-nitro-2-(3-phenylpropylami no)benzoic acid, 2.5 mM diphenylamine-2-carboxylate, and 500 mu M DIDS and thus mediated through Ca2+-activated Cl- channels. Histamine-stim ulated I-125(-) efflux was 1) inhibited by 100 mu M diphenhydramine, a n H-1 receptor antagonist, 2) resistant to 1 mM cimetidine, an H-2 rec eptor antagonist, 3) not reproduced by 1 mM dimaprit, an H-2 agonist, and 4) inhibited by 50 mu M ,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tet raacetic acid-AM, a Ca2+ chelator, suggesting that it was mediated thr ough H-1 receptors acting via increased cytosolic Ca2+. Histamine also stimulated a Rb-86(+) efflux that was sensitive to 100 nM charybdotox in and thus mediated through Ca2+-activated K+ channels. When PDEC mon olayers were studied in Ussing chambers, a short-circuit current of 21 .7 +/- 3.1 mu A/cm(2) was stimulated by 100 mu M histamine. This effec t was inhibited by diphenhydramine but not cimetidine, was not reprodu ced with dimaprit, and was observed only after serosal addition of his tamine, suggesting that it was mediated by basolateral H-1 receptors o n PDEC. In conclusion, histamine, acting through basolateral H-1 recep tors, activates both Ca2+-activated Cl- and K+ channels; in this manne r, it may regulate PDEC secretion in normal or inflamed pancreas.