AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 4 509-G517, Copyright © 1986 by American Physiological Society

ARTICLES

Effects of phorbol esters on sodium and chloride transport in rat colon

M. Donowitz, H. Y. Cheng and G. W. Sharp

To determine the role of protein kinase C in the regulation of active electrolyte transport in rat descending colon, the effects of phorbol dibutyrate (PDB) were studied using the Ussing chamber/voltage-clamp technique. PDB added to the serosal surface increased the short-circuit current in a concentration dependent manner with a EC50 of 3 X 10(-8) M and a maximal effect at 10(-7) M PDB. The effect was not seen with the inactive alpha-phorbol analogue but was reproduced with 1-oleoyl-2-acetylglycerol, a more permeable analogue of diacylglycerol. PDB caused a decrease in mucosal-to-serosal and net fluxes of Na and Cl and an increase in serosal-to-mucosal Cl flux, indicating inhibition of Na and Cl absorption and stimulation of Cl secretion. The PDB-induced increase in Cl secretion was virtually abolished by both indomethacin and ibuprofen, indicating a dependence on arachidonic acid metabolism via the cyclooxygenase pathway. The Cl secretion was inhibited by verapamil and Ca2+-free bathing solution on the serosal surface but not by dantrolene, suggesting the importance of extracellular Ca2+ but not intracellular stored Ca2+ in the PDB-induced secretion. The Cl secretory effect was also inhibited by tetrodotoxin and atropine, suggesting involvement of cholinergic nerves. In contrast, the PDB-induced decrease in Na and Cl absorption was not dependent on metabolites of the cyclooxygenase pathway, not dependent on extracellular Ca2+, and not blocked by tetrodotoxin. It appears likely that protein kinase C is involved in the regulation of rat colonic active Na and Cl absorption and electrogenic Cl secretion but that the pathways involved are different in the two transport systems.

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