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 mucosal bicarbonate secretion was investigated in the guinea pig. In a series of experiments in vivo, the duodenum was perfused with 24 mmol/liter NaHCO₃ solution (+ NaCl for isotonicity) to ensure that active duodenal HCO₃^- secretion against a concentration gradient was measured. Acetazolamide (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 decreased HCO₃^- secretion after stimulation with dibutyryl 5′-cyclic adenosine monophosphate (dBcAMP, 10^-5 mol/kg), dibutyryl 5′-cyclic guanosine monophosphate (dBcGMP, 10^-5 mol/kg), prostaglandin E₂ (PGE₂, 10^-6 mol/kg), PGF_2α (10^-6 mol/kg), tetradecanoyl-phorbol-acetate (TPA, 10^-7 mol/kg), glucagon (10^-7 mol/kg), vasoactive intestinal polypeptide (VIP, 10^-8 mol/kg), and carbachol (10^-8 mol/kg). Utilizing a fluorescence technique, we could detect the enzyme carbonic anhydrase in equal amounts in villous and crypt cells of the proximal duodenal epithelium; no activity was demonstrated in tissues pretreated with acetazolamide. In conclusion, carbonic anhydrase is required for both basal and stimulated duodenal HCO₃^- secretion.