Endotoxin-induced alterations in rat colonic water and electrolyte transport.
This study examines the effects of endotoxin on intestinal water and electrolyte transport in adult male rats. Endotoxin (1.55 mg/kg, intravenously) reduced in vivo colonic saline absorption 61% in 1 hour. In vitro unidirectional and net 22Na and 36Cl fluxes showed that endotoxin significantly decreased net colonic 22Na absorption compared with control colons (0.3 +/- 1.7 vs. 4.8 +/- 1.1 microEq/h x cm2). Although endotoxin had no significant effect on basal short circuit current (Isc) and conductance, 3H-inulin flux studies suggested an increase in colonic permeability. Isc responses to the 5'-cyclic adenosine monophosphate (cAMP)-dependent secretagogues prostaglandin E2 (1 mumol/L) and vasoactive intestinal peptide (0.1 mumol/L) were diminished by 80% and 50%, respectively. However, cytosolic cAMP-dependent protein kinase activity under basal and stimulated (6 mumol/L 8-bromo-cAMP) conditions was not altered by endotoxin treatment. The Isc responses to 10 mumol/L bethanechol, a Ca(2+)-dependent agonist, were not effected by endotoxin treatment. It was concluded that endotoxin significantly affects colonic transport function and may contribute to the development of diarrhea in inflammatory bowel diseases.
University of Chicago, Department of Medicine, Illinois.
M J
MJ
Ciancio
L
L
Vitiritti
A
A
Dhar
E B
EB
Chang
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D001692:Biological Transport; D002713:Chlorine / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003967:Diarrhea / Q000503:physiopathology; D015232:Dinoprostone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D007082:Ileum / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D011494:Protein Kinases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000493:pharmacokinetics; D013806:Theophylline / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D001626:Bethanechol Compounds; D004731:Endotoxins; D007328:Insulin; D018723:Bethanechol; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D002713:Chlorine; D012964:Sodium; D013806:Theophylline; D011494:Protein Kinases; D015232:Dinoprostone