Is nitric oxide involved in 5-HT-induced fluid secretion in the gut?
The present study was undertaken to test the hypothesis that 5-HT stimulates nitric oxide (NO) generating neurons, and that these neurons participate in the mediation of 5-HT-induced fluid secretion. 5-HT induced electrogenic Cl- secretion in guinea-pig distal colon. This response was abolished by tetrodotoxin but not by atropine. The maximum response to 5-HT (10(-5) M) was inhibited by approximately 65% (P < 0.05, n = 6) by the NO synthase inhibitor, NG-nitro-L-arginine (L-NNA, 10(-4) M). The substrate of NO synthase, L-Arg (10(-3) M) reversed the inhibition of 5-HT-induced secretions by L-NNA. 5-HT-induced diarrhea in fasted mice was reduced by atropine in vivo. NG-Nitro-L-Arg methyl ester (L-NAME, 1-32 mg/kg, i.p.) dose-dependently inhibited 5-HT (1 mg/kg)-induced diarrhea. The inhibitory effect of L-NAME was reversed by L-Arg, but not D-Arg (600 mg/kg, i.p., respectively). Taken together, these data suggest that 5-HT-induced fluid secretion in the gut is partly due to the activation of neurons that generate NO.
Kadowaki
M
M
Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA.
Gershon
M D
MD
Kuwahara
A
A
D000818:Animals; D001826:Body Fluids / Q000502:physiology; D003967:Diarrhea / Q000139:chemically induced / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism; D004068:Digestive System Physiological Phenomena; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester