Guanylin strongly stimulates rat duodenal HCO3- secretion: proposed mechanism and comparison with other secretagogues.
OBJECTIVE
Guanylin and heat-stable enterotoxin (STa) stimulate intestinal Cl- secretion via activation of the cystic fibrosis transmembrane 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 duodenal 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 3H-mannitol fluxes, bidirectional 36Cl- 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 Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate, and additive to the HCO3- secretory rate stimulated by glucagon and carbachol but not by the tested adenosine 3',5'-cyclic monophosphate (cAMP)-dependent agonists. The ratio of the HCO3- secretory rate/Isc stimulated by the tested guanosine 3',5'-cyclic monophosphate (cGMP)-dependent agonists was markedly higher than the cAMP-dependent agonists. Prostaglandin E2 and 8-bromo-cAMP but not STa/guanylin also transiently increased paracellular permeability.


CONCLUSIONS
Guanylin and STa stimulate electrogenic HCO3- secretion in rat duodenum, most likely via CFTR Cl- channel activation, but the different relationship for HCO3- to Isc in cGMP-than in cAMP-stimulated anion secretion suggests a different cellular source and/or signaling pathways.
Guba
M
M
First Department of Medicine, Eberhard-Karis-Universität Tübingen, Germany.
Kuhn
M
M
Forssmann
W G
WG
Classen
M
M
Gregor
M
M
Seidler
U
U
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport; D004386:Duodenum / Q000378:metabolism*; D004768:Enterotoxins / Q000378:metabolism*; D005260:Female; D005768:Gastrointestinal Hormones; D006863:Hydrogen-Ion Concentration; D045265:Natriuretic Peptides; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001639:Bicarbonates; D004768:Enterotoxins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; C072685:guanylin