Identification of agonists of duodenal alkaline secretion.

This report describes approaches for accurate determination of the comparative activities of stimulants of duodenal alkaline secretion. We screened about 200 standard pharmacological agents using a bullfrog-isolated mucosal preparation in order to characterize fully the mechanisms of duodenal alkaline secretion. A variety of eicosanoids, phosphodiesterase (PDE) inhibitors, adrenoreceptor agonists and benzodiazepines, together with forskolin, 6-hydroxydopamine, 2-chloroadenosine, dipyridamole, dihydropyridazinone and testosterone, caused a reproducible increase in the metabolism-dependent component of duodenal alkaline secretion. Prostaglandin E2 (ED50 of 0.02 micrograms ml-1 in vitro) was the most potent and efficacious stimulant in the isolated mucosa and in the perfused cat duodenum in vivo. In the isolated duodenum, the predominant mechanism for stimulating alkaline secretion appears to be via elevation of intracellular cAMP levels, but in vivo indirect effects, for example on mucosal blood flow, may determine the overall influence of agents on duodenal alkalinization.