ROLE OF CARBONIC-ANHYDRASE IN BASAL AND STIMULATED BICARBONATE SECRETION BY THE GUINEA-PIG DUODENUM

The role of carbonic anhydrase in the process of proximal duodenal muc osal bicarbonate secretion was investigated in the guinea pig. In a se ries of experiments in vivo, the duodenum was perfused with 24 mmol/li ter NaHCO3 solution (+ NaCl for isotonicity) to ensure that active duo denal HCO3- secretion against a concentration gradient was measured. A cetazolamide (80 mg/kg) was infused intravenously to examine the role of carbonic anhydrase on basal and agonist-stimulated HCO3- secretion. Acetazolamide abolished basal HCO3- secretion and significantly decre ased HCO3- secretion after stimulation with dibutyryl 5'-cyclic adenos ine monophosphate (dBcAMP, 10(-5) mol/kg), dibutyryl 5'-cyclic guanosi ne monophosphate (dBcGMP, 10(-5) mol/kg), prostaglandin E(2) (PGE(2), 10(-6) mol/kg), PGF(2 alpha) (10(-6) mol/kg), tetradecanoyl-phorbol-ac etate (TPA, 10(-7) mol/kg), glucagon (10(-7) mol/kg), vasoactive intes tinal polypeptide (VIP, 10(-8) mol/kg), and carbachol (10(-7) mol/kg). Utilizing a fluorescence technique, we could detect the enzyme carbon ic anhydrase in equal amounts in villous and crypt cells of the proxim al duodenal epithelium; no activity was demonstrated in tissues pretre ated with acetazolamide. In conclusion, carbonic anhydrase is required for both basal and stimulated duodenal HCO3- secretion.