Cyclic adenosine monophosphate is the second messenger of prostaglandin E2- and vasoactive intestinal polypeptide-stimulated active bicarbonate secretion by guinea-pig duodenum.
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 2 alpha (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 PGF2 alpha 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 the PGE2 and VIP cause bicarbonate secretion by the serial activation of adenylate cyclase and protein kinase A in duodenal epithelial cells.
Reimer
R
R
Institute of General Pharmacology, Medical School, Hanover, Germany.
Odes
H S
HS
Muallem
R
R
Schwenk
M
M
Beil
W
W
Sewing
K F
KF
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D015290:Second Messenger Systems; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D001639:Bicarbonates; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D015232:Dinoprostone