The role of nitric oxide (NO) in 5-HT-induced relaxations of the guinea-pig stomach.
In a previous study we showed that the relaxations induced after vagal stimulation of the guinea-pig stomach are mediated via nitric oxide (NO) or a NO-related substance. Intra-arterial injection (i.a.) of 5-hydroxytryptamine (5-HT) also induced relaxations in the guinea-pig stomach. Since it has been shown that in the guinea-pig colon 5-HT-induced relaxations are mediated via NO the aim of this study was to establish whether NO is involved in the 5-HT-induced relaxations in the guinea-pig stomach. Intra-arterial injection of 5-HT induced dose-dependent relaxations of the stomach. Since atropine and alpha- and beta-adrenoceptor blocking agents did not influence the relaxation and since tetrodotoxin (TTX) blocked the relaxations, this effect is mediated via NANC-neurons. Administration of a NO-synthase-inhibitor NG-nitro-L-arginine (L-NNA) concentration-dependently reduced the 5-HT-induced relaxations. Haemoglobin (a NO-scavanger) did not affect the relaxations to 5-HT, while addition of methylene blue, an inhibitor of soluble guanylate cyclase, reduced the relaxations by 50%. Addition of an opioid receptor agonist (loperamide), a 5-HT1 antagonist (methiothepin or metergoline) or a 5-HT4 receptor agonist (cisapride) or -antagonist (tropisetron in micromolar concentrations) inhibited the 5-HT-induced relaxations. Neither the 5-HT4 receptor agonist renzapride, nor the novel 5-HT4 receptor antagonist SDZ 205-557, affected the relaxations to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Meulemans
A L
AL
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Helsen
L F
LF
Schuurkes
J A
JA
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D013270:Stomach / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D013779:Tetrodotoxin; D001285:Atropine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases