Facilitation by substance P and inhibition by (+)-tubocurarine of the 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats.
The influence of substance P 3 (microgram/kg) and (+)-tubocurarine (850 micrograms/kg) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. The Bezold-Jarisch reflex was induced by the 5-HT3 receptor agonist phenylbiguanide (0.3, 1, 3 and 10 micrograms/kg i.v.) and by capsaicin (10 micrograms/kg i.v.). The 5-HT3 receptor antagonist ondansetron (10 micrograms/kg) abolished the phenylbiguanide- but not the capsaicin-stimulated bradycardia, indicating that phenylbiguanide and capsaicin act via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Substance P significantly potentiated the phenylbiguanide- but not the capsaicin-induced decrease in heart rate. Also, when the phenylbiguanide-induced response was amplified by substance P, it was abolished by ondansetron. (+)-Tubocurarine inhibited the phenylbiguanide-induced bradycardia, but did not affect the capsaicin-stimulated decrease in heart rate. Our results demonstrate that substance P potentiates but (+)-tubocurarine inhibits the 5-HT3 receptor-mediated Bezold-Jarisch reflex. Both effects are probably due to direct influences of the drugs on the 5-HT3 receptors on sensory vagal nerves in the heart.
Malinowska
B
B
Zaklad Farmakodynamiki, Akademia Medyezna, Bialystok, Poland.
Godlewski
G
G
Buczko
W
W
Göthert
M
M
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012018:Reflex / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*; D014403:Tubocurarine / Q000494:pharmacology*
D003473:Neuromuscular Nondepolarizing Agents; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D013373:Substance P; D002211:Capsaicin; D014403:Tubocurarine