Differential role of cyclic GMP–dependent protein kinase II in ion transport in murine small intestine and colon
AB Vaandrager, AGM Bot, P Ruth, A Pfeifer, F Hofmann… - Gastroenterology, 2000 - Elsevier
AB Vaandrager, AGM Bot, P Ruth, A Pfeifer, F Hofmann, HR De Jonge
Gastroenterology, 2000•ElsevierBackground & Aims: The aim of this study was to determine the role of guanosine 3', 5'-cyclic
monophosphate (cGMP)-dependent protein kinase (cGK) type II in intestinal fluid
homeostasis under basal conditions and following exposure to cGMP-linked secretagogues,
eg, Escherichia coli heat-stable enterotoxin (STa) and guanylin. Methods: Fluid and ion
transport was determined in different segments of the intestine of wild-type and cGK II–
deficient mice by ligated loop assays in vivo, and by short-circuit current and isotope flux …
monophosphate (cGMP)-dependent protein kinase (cGK) type II in intestinal fluid
homeostasis under basal conditions and following exposure to cGMP-linked secretagogues,
eg, Escherichia coli heat-stable enterotoxin (STa) and guanylin. Methods: Fluid and ion
transport was determined in different segments of the intestine of wild-type and cGK II–
deficient mice by ligated loop assays in vivo, and by short-circuit current and isotope flux …
Background & Aims
The aim of this study was to determine the role of guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (cGK) type II in intestinal fluid homeostasis under basal conditions and following exposure to cGMP-linked secretagogues, e.g., Escherichia coli heat-stable enterotoxin (STa) and guanylin.
Methods
Fluid and ion transport was determined in different segments of the intestine of wild-type and cGK II–deficient mice by ligated loop assays in vivo, and by short-circuit current and isotope flux measurements in vitro.
Results
Small intestinal fluid absorption in vivo was enhanced in cGK II–deficient mice under basal conditions and in the presence of STa. Furthermore, STa, guanylin, and 8-pCPT-cGMP stimulation of electrogenic anion secretion and inhibition of Na+ absorption in vitro were markedly reduced in the small intestine from cGK II −/− mice but not in proximal colon. The type III phosphodiesterase inhibitor amrinone mimicked STa action in cGK II −/− mice, and also stimulated ion secretion in humans.
Conclusions
This study shows that the cGMP/cGK II pathway regulates fluid homeostasis in the small intestine under basal conditions and mediates STa effects by both increasing anion secretion and inhibiting Na+ absorption. It also demonstrates the presence of a cGK II–independent pathway for STa/cGMP-provoked secretion predominantly in the colon, which possibly involves a cGMP-inhibitable phosphodiesterase and/or activation of the cAMP–dependent protein kinase pathway. GASTROENTEROLOGY 2000;118:108-114
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