Alkaline secretion by amphibian duodenum. III. Effect of DBcAMP, theophylline, and prostaglandins

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Abstract
The effects of dibutyryl cAMP (DBcAMP), theophylline, prostaglandin E1 (PGE1), PGE2, 16,16-dimethyl PGE2 (16,16-dmPGE2) and PGF2.alpha. on short-circuit current (Isc), alkaline secretion, tissue electrical resistance and fluxes of Na+ and Cl- in short-circuited amphibian [Rana catesbeiana] duodenal mucosa in vitro were examined. Addition of DBcAMP (10-4 to 10-3 M) caused a rapid sustained rise in Isc to 155 .+-. 6% of control values. This was accomplished by a slower but ultimately equal rise in alkaline secretion to 162 .+-. 8% of control. The response to DBcAMP was not different in the absence of Cl-, was reduced by 60% in the absence of Na+ and was totally abolished in the absence of HCO3- and CO2. The effects of DBcAMP could be reproduced by 10-2 M theophylline, 10-6 M PGE1, 10-6 M PGE2, 10-5 M 16,16-dmPGE2 or 10-4 M PGF2.alpha.. Minimal effective concentrations were 10-9 to 10-8 M PGE1, 10-10 M PGE2, 10-9 to 10-9 to 10-8 M 16,16-dmPGE2, 10-7 to 10-6 M PGF2.alpha. and 10-5 M DBcAMP. There was a highly significant correlation between the increase in Isc and the increase in the rate of alkaline secretion. Each agent reduced tissue electrical resistance probably by increasing the conductance of both transcellular and paracellular pathways. There was no summation between DBcAMP, theophylline and PGE1 or PGE2, and the increase in Isc was saturable. Neither DBcAMP nor PGE2 affected net fluxes of Na+ or Cl-, though these agents increased both unidirectional fluxes of Cl-, suggesting altered permselectivity of the paracellular shunt. The effect of PGE2 on Isc was not different in the presence or absence of a transmucosal HCO3- gradient and was abolished by 5 .times. 10-5 M ouabain in the nutrient solution. Increased intracellular cAMP stimulates the electrogenic, active, Na+-dependent secretion of alkali without affecting net transport of Na+ or Cl- and that cAMP may act as a 2nd messenger in duodenal alkaline secretion.