Cyclic adenosine monophosphate is the second messenger of prostaglandin e₂- and vasoactive intestinal polypeptide-stimulated active bicarbonate secretion by Guinea-pig duodenum

Reimer R, Odes HS, Muallem R, Sehwenk M, Beil W, Sewing K-Fr. Cyclic adenosine monophosphate is the second messenger of prostaglandin E₂- and vasoactive intestinal polypeptide-stimulated active bicarbonate secretion by guinea-pig duodenum. Scand J Gastroenterol 1994;29:153-159. In a guinea-pig model we determined the intracellular events mediating the response of duodenal epithelial cells to vasoactive intestinal polypeptide (VIP) and prostaglandin (PG) E₂. Intravenous administration of VIP (10^-9 to 10^-7 mol/kg) and PGE₂ (10^-9 to 10^-6 mol/kg) dose-dependently increased duodenal epithelial bicarbonate secretion against an HCO₃ concentration gradient, measured by a luminal perfusion technique, in anaesthetized guinea-pigs up to 4.5-fold. This secretion could be mimicked by intraduodenal dibutyryl cyclic adenosine monophosphate (dBcAMP; 10^-9 to 10^-7 mol/kg). Secretin (10^-9 mol/kg) and PGF_2α (10^-9 to 10^-7 mol/kg), both given intravenously, were without effect or considerably less efficient. For VIP and PGE₂, specific receptors coupled to adenylate cyclase could be demonstrated in homogenates of isolated duodenal epithelial cells. VIP and PGE₂ stimulated adenylate cyclase activity up to sixfold, whereas PGF_2α and secretin were considerably less potent and efficient. VIP and PGE₂ increased intracellular cyclic AMP levels up to fivefold and ninefold, respectively. This was followed by an increase in cytosolic protein kinase A activity. Bicarbonate secretion was maximal at 30 min. Examination of the subcellular distribution of protein kinase A showed a predominant cytosolic location. These data support the notion that PGE₂ and VIP cause bicarbonate secretion by the serial activation of adenylate cyclase and protein kinase A in duodenal epithelial cells.