GUANYLIN STRONGLY STIMULATES RAT DUODENAL HCO3- SECRETION - PROPOSED MECHANISM AND COMPARISON WITH OTHER SECRETAGOGUES

Background & Aims: Guanylin and heat-stable enterotoxin (STa) stimulat e intestinal Cl- secretion via activation of the cystic fibrosis trans membrane regulator (CFTR)-encoded Cl- channel, it was speculated that CFTR activation also regulates electrogenic duodenal HCO3- secretion. Therefore, the effect of guanylin/STa and other secretagogues on rat d uodenal HCO3- secretion was studied, Methods: The HCO3- secretory rate of in vitro rat proximal duodenum was determined by pH stat titration and paracellular permeability by H-3-mannitol fluxes, bidirectional C l-36(-) fluxes were measured, and the short-circuit current (Isc) was recorded, Results: Luminal guanylin and STa concentration dependently stimulated the HCO3- secretory rate and Isc, Guanylin-stimulated HCO3- secretion was independent of luminal Cl, inhibited by the CI channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate, and additive to the H CO3- secretory rate stimulated by glucagon and carbachol but not by th e tested adenosine 3',5'-cyclic monophosphate (cAMP)-dependent agonist s. The ratio of the HCO3- secretory rate/Isc stimulated by the tested guanosine 3',5'-cyclic monophosphate (cGMP)-dependent agonists was mar kedly higher than the cAMP-dependent agonists. Prostaglandin E(2) and 8-bromo-cAMP but not STa/guanylin also transiently increased paracellu lar permeability. Conclusions: Guanylin and STa stimulate electrogenic HCO3- secretion in rat duodenum, most likely vie CFTR Cl- channel act ivation, but the different relationship for HCO3- to Isc in cGMP- than in cAMP-stimulated anion secretion suggests a different cellular sour ce and/or signaling pathways.