Effect of E. coli heat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice.
We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3- Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+ absorption, lower net Cl- absorption, and a negative residual ion flux (J(R)), indicating net HCO3- absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl- (J(s-->m)(Cl)) and decreased net Cl- flux (J(net)(Cl)) accompanied by increases in short-circuit current (I(sc)), potential difference (PD), and tissue conductance (G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon J(s-->m)(Cl) and J(net)(Cl), I(sc), PD, G, and J(R) similar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa.
Charney
A N
AN
Nephrology Section, Veterans Affairs Medical Center, 423 E. 23rd Street, New York, NY 10010, USA.
Egnor
R W
RW
Alexander-Chacko
J T
JT
Zaharia
V
V
Mann
E A
EA
Giannella
R A
RA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004355:Drug Stability; D004553:Electric Conductivity; D004768:Enterotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006162:Guanylate Cyclase; D006358:Hot Temperature; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide; D012016:Reference Values; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D004768:Enterotoxins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C016276:8-bromocyclic GMP; D012964:Sodium; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D006152:Cyclic GMP