Facilitation by substance P and inhibition by (+)-tubocurarine of the 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats

European Journal of Pharmacology
B MalinowskaM Göthert

Abstract

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.

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Citations

Feb 20, 2003·European Journal of Pharmacology·David PascualMaría Isabel Martín
Jun 18, 2003·Respiratory Physiology & Neurobiology·Jay K HermanGerald E Bisgard
May 8, 1999·The British Journal of Dermatology·U Wollina
Feb 24, 2012·Pharmacological Reports : PR·Sebastian Ł LupińskiBarbara Malinowska
Dec 29, 1998·The Journal of Trauma·R J GuyG J Cooper
May 16, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·H BönischE Schlicker

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