NN'-dicyclohexylcarbodiimide (DCCD) reduces pancreatic NaHCO3 secretion without changing pancreatic tissue ATP levels.
To study the mechanism responsible for pancreatic NaHCO3 secretion, the inhibitor NN'-dicyclohexylcarbodiimide (DCCD) was administered to six secretin-infused, anaesthetized pigs. Pancreatic juice was collected from a catheter in the main pancreatic duct. Secretion rate was measured at several arterial pH values in each animal, both before and after DCCD. 15 (14-30) mumol kg-1 body wt DCCD, intra-arterially, reduced pancreatic NaHCO3 secretion from 296 (234-398) to 181 (134-237) mumol min-1 at arterial pH 7.43 (7.42-7.47). Similar fractional reductions of secretion occurred at lower arterial pH. Pancreatic tissue ATP concentration, 1.8 (1.4-2.0) mumol g-1 wet wt, was not changed by DCCD. DCCD, less than or equal to 10(-4) mol l-1, did not change Na,K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. It is concluded that DCCD reduced pancreatic NaHCO3 secretion by a mechanism not involving ATP depletion nor inhibition of Na,K-ATPase nor carbonic anhydrase activities in pancreatic cells. Because DCCD inhibits proton pumps, DCCD may have reduced NaHCO3 secretion through interfering with a proton pump involved in extruding H+ from HCO-3 secreting cells to interstitial fluid in the pancreas.
D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002234:Carbodiimides / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D010179:Pancreas / Q000187:drug effects*; D010189:Pancreatic Juice / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
D001639:Bicarbonates; D002234:Carbodiimides; D012633:Secretin; D004024:Dicyclohexylcarbodiimide; D000255:Adenosine Triphosphate; D002256:Carbonic Anhydrases; D000254:Sodium-Potassium-Exchanging ATPase