Involvement of K+ channel modulation in the proabsorptive effect of nitric oxide in the rat jejunum in vivo.
The role of K+ channels in the mediation of the nitric oxide(NO)-induced proabsorptive effect in intestinal fluid transport was investigated in a functional study, using a model of ligated jejunal loops of anaesthetized rats in vivo. The K+ channel opener cromakalim and the K+ channel blocker glibenclamide were administered under basal conditions as well as under conditions, when fluid secretion was influenced by N omega-nitro-L-arginine methyl ester (L-NAME), prostaglandin E2, Escherichia coli heat stable enterotoxin a (E. coli STa) or L-arginine. Intravenous infusion of cromakalim (63.5 micrograms/kg per min) significantly enhanced net fluid absorption compared to controls, totally abolished net fluid secretion induced by L-NAME (0.55 mg/kg per min), reversed net fluid secretion induced by intraluminal instillation of E. coli STa (10 units/ml) to absorption, but did not influence fluid secretion elicited by close i.a. infusion of prostaglandin E2 (79 ng/min). Close i.a. infusion of glibenclamide (0.16 mg/kg per min) reversed net fluid absorption to net secretion, blocked the absorptive effect of L-arginine (8.88 mg/kg per min) and reduced the proabsorptive effect of cromakalim. The secretory effect of L-NAME was not further enhanced by glibenclamide. These results suggest that modulation of basolateral K+ channels by NO is involved in the mediation of its proabsorptive effect, since opening and closure of K+ channels mimicked, respectively counteracted, the action of NO-donors and inhibitors of NO-synthesis on intestinal fluid transport. The role of prostaglandins in the proabsorptive effect of NO remains to be elucidated. These results furthermore support the role of K+ channel openers as potential new antidiarrheal drugs.
Schirgi-Degen
A
A
Department of Experimental and Clinical Pharmacology, Karl-Franzens-University of Graz, Austria.
Beubler
E
E
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001692:Biological Transport; D019806:Cromakalim; D005260:Female; D007583:Jejunum / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009569:Nitric Oxide