5-Hydroxytryptamine3 receptors mediate tachycardia in conscious instrumented dogs

H Wilson, WJ Coffman and ML Cohen

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.

Intravenously administered 5-HT and the 5-HT3 selective agonist, 2CH3-5- HT, and the 5-HT2 selective agonist, alpha-CH3-5-HT, transiently increased heart rate in conscious, instrumented dogs. 5-HT, alpha-CH3-5- HT and 2CH3-5-HT increased systolic blood pressure in conscious dogs. The increase in blood pressure produced by alpha-CH3-5-HT was blocked by the 5-HT2 selective antagonist, LY53857, supporting a role for vascular 5-HT2 receptors in the pressor response to these amines. In contrast, LY53857 did not antagonize tachycardia produced by 2CH3-5-HT. Furthermore, propranolol also did not block 2CH3-5-HT-induced tachycardia, indicating that an indirect neuronal effect to release norepinephrine cannot explain the increase in heart rate to 2CH3-5-HT. Tachycardia to 2CH3-5-HT (as well as to isoproterenol) was modestly inhibited, but never abolished by interruption of the autonomic nervous system with atropine or hexamethonium. 5-HT3 receptor antagonists, zacopride, ICS 205-930 and GR38032F, dose-dependently blocked the tachycardia and pressor response to 2CH3-5-HT. These data establish the presence of a 5-HT3 receptor mediating a direct positive chronotropic effect of 5-HT in conscious dogs, an effect that depends, only minimally, on the presence of an intact autonomic nervous system.

Volume 252, Issue 2, pp. 683-688, 02/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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