Selected Publication:
Schirgi-Degen, A; Beubler, E.
Involvement of K+ channel modulation in the proabsorptive effect of nitric oxide in the rat jejunum in vivo.
Eur J Pharmacol. 1996; 316(2-3):257-262
Doi: 10.1016%2FS0014-2999%2896%2900683-8
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- Leading authors Med Uni Graz
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Beubler Eckhard
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- Abstract:
- 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.
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Animals -
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Benzopyrans - pharmacology
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Biological Transport - pharmacology
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Cromakalim - pharmacology
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Female - pharmacology
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Jejunum - drug effects
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Nitric Oxide - pharmacology
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Potassium Channels - drug effects
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Pyrroles - pharmacology
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Rats - pharmacology
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Rats, Sprague-Dawley - pharmacology
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Vasodilator Agents - pharmacology
- Find related publications in this database (Keywords)
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Intestinal Fluid Transport
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Nitric Oxide (No)
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N-Omega-Nitro-L-Arginine Methyl Ester(L-Name)
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K+ Channels
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Prostaglandin E(2)
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Escherichia Coli Enterotoxin-Induced Secretion