Ondansetron facilitates neuromuscular transmission in the guinea-pig ileum.
The effects of ondansetron on the neuromuscular function of the guinea-pig ileum were investigated in vitro. Ondansetron, but not tropisetron or MDL 72222 (1alpha-H-3alpha-5alpha-H-tropan-3-yl-3,5-dichlo robenzoate), enhanced submaximal electrically induced contractions (EC50) = 1.3 x 10(-5) M). Desensitization with 5-hydroxytryptamine (1 x 10(-5) M) or 2-methyl-5-HT (1 x 10(-5) M) abolished this facilitatory response, which remained unaltered after desensitization with 5-methoxytryptamine (1 x 10(-5) M) or addition of tropisetron, MDL 72222, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan, SB203186 (1-piperidinylethyl-1H-indole-3 carboxylate hydrochloride), pirenzepine or hexamethonium. At higher concentrations, ondansetron decreased the electrically induced contractions (EC50 = 1 x 10(-4) M); the inhibitory response was unaffected by (-)-naloxone (1 x 10(-6) M) or idazoxan (1 x 10(-6) M). We conclude that, in the guinea-pig ileum, ondansetron elicits a biphasic response: facilitation of neuromuscular transmission mediated by a serotonergic receptor distinct from the 5-HT3, 5-HT4 or putative 5-HT1P receptors, and an inhibitory response that does not involve opiate or alpha2-adrenoceptors.
González
A A
AA
Anesthesiology Research Unit, IMIM, Department of Anesthesiology, Hospital Universitario del Mar, Barcelona, Spain.
Puig
M M
MM
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D017294:Ondansetron / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014326:Tropanes / Q000494:pharmacology; D000077526:Tropisetron
C088817:(1-piperidinyl)ethyl 1H-indole-3-carboxylate; D007211:Indoles; D010880:Piperidines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D014326:Tropanes; D012701:Serotonin; D008735:5-Methoxytryptamine; D017294:Ondansetron; D000077526:Tropisetron; C045918:2-methyl-5-HT; C042253:bemesetron