Effects of histamine and histamine receptor antagonists on ion transport in rabbit descending colon

R. D. McCabe, P. L. Smith

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The effects of histamine on colonic ion transport were examined in in vitro preparations of rabbit descending colon. Serosal addition of histamine (10-5 M) produced a transient increase in short-circuit current [I(sc)] and transepithelial conductance. The I(sc) response to histamine could be blocked by removing Cl from both bathing solutions, adding furosemide (10-3 M) to the serosal bathing solution, adding indomethacin to the serosal and mucosal bathing solutions (10-5 M), or removing Ca from the serosal bathing solution. In addition, the histamine-induced increase in I(sc) was inhibited in a dose-dependent manner by the H1-receptor antagonist diphenhydramine, with a maximal inhibition at 10-4 M and a half-maximal inhibition at 3 x 10-7 M. The H2-receptor antagonist cimetidine (10-3 M) was without effect on the histamine response. Measurement of unidirectional Na, K, and Cl fluxes revealed that serosal addition of diphenhydramine (10-3 M) reduced basal I(sc) due to a decrease in mucosal-to-serosal Na flux. Serosal addition of diphenhydramine (10-3 M) also inhibited the increase in I(sc) produced by serosal addition of prostaglandin E1, 8-bromo-cAMP, cholera toxin, or the ionophore A23187. Measurement of unidirectional K and Cl fluxes revealed that prostaglandin E1 alone increased serosal-to-mucosal K and Cl fluxes and reduced the mucosal-to-serosal K flux, thereby increasing net K and Cl secretion. Serosal diphenhydramine (10-3 M) abolished the changes in Cl fluxes produced by prostaglandin E1 and reduced the magnitude of the changes in K fluxes. This study suggests that ion transport by rabbit descending colon is altered by histamine via H1-receptors.

Original languageEnglish
Pages (from-to)G411-G418
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number4
StatePublished - 1984


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