Differential role of cyclic GMP-dependent protein kinase II in ion transport in murine small intestine and colon

Gastroenterology. 2000 Jan;118(1):108-14. doi: 10.1016/s0016-5085(00)70419-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / pharmacology
  • Colon / drug effects
  • Colon / metabolism*
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / pharmacology
  • Cyclic GMP-Dependent Protein Kinase Type II
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Enterotoxins / pharmacology
  • Enzyme Activators / pharmacology
  • Escherichia coli Proteins
  • Gastrointestinal Hormones*
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Ion Transport* / drug effects
  • Mice
  • Natriuretic Peptides
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Thionucleotides / pharmacology


  • Bacterial Toxins
  • Enterotoxins
  • Enzyme Activators
  • Escherichia coli Proteins
  • Gastrointestinal Hormones
  • Natriuretic Peptides
  • Peptides
  • Thionucleotides
  • heat stable toxin (E coli)
  • guanylin
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-GMP
  • Cyclic GMP-Dependent Protein Kinase Type II
  • Cyclic GMP-Dependent Protein Kinases
  • PRKG2 protein, human
  • Prkg2 protein, mouse
  • Cyclic GMP