Nitric oxide-donating compounds stimulate electrolyte transport in the guinea pig intestine in vitro.
The role of nitric oxide (NO) as a regulator of intestinal electrolyte transport was investigated in stripped segments of guinea pig intestine mounted in Ussing chambers. Serosal application of the NO-donating compounds sodium nitroprusside or isosorbide dinitrate (in the presence of 5 microM L-cysteine) resulted in concentration-dependent increases in the short circuit current. The response to 0.5 mM nitroprusside was exhibited to the same degree in duodenum, jejunum, ileum and proximal colon, and to a lesser degree in the distal colon. The response to nitroprusside was reduced by pretreatment with either the cyclo-oxygenase inhibitor, indomethacin (45% inhibition), the 5-HT3 antagonist, BRL43694 (30% inhibition) or by incubation with chloride-free buffer (59% inhibition). There was no significant effect of the 5-HT2 receptor antagonist, LY53857, or the neural blocker, tetrodotoxin. Pretreatment of ileal segments with the NO synthase inhibitor, NG-monomethyl-L-arginine, did not significantly alter the short circuit current response to electrical field stimulation compared to controls. Exposure of ileal mucosal scrapings to sodium nitroprusside resulted in a significant increase in cGMP production. The data suggest that exogenous NO-donating compounds can modulate electrolyte transport in the guinea pig intestine in vitro. The response is cyclo-oxygenase-, 5-HT3- and chloride-dependent, and coincides with increases in mucosal cGMP. However, the role of endogenous NO in regulating electrolyte transport remains unclear.
MacNaughton
W K
WK
Department of Physiology, University of Ottawa, Ontario, Canada.
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D006152:Cyclic GMP / Q000032:analysis; D004573:Electrolytes / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology
D004573:Electrolytes; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate