5-Hydroxytryptamine3 receptors mediate tachycardia in conscious instrumented dogs.
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.
Wilson
H
H
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
Coffman
W J
WJ
Cohen
M L
ML
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004285:Dogs; D004873:Ergolines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017294:Ondansetron; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D000077526:Tropisetron
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004873:Ergolines; D006584:Hexamethonium Compounds; D007093:Imidazoles; D007211:Indoles; D011985:Receptors, Serotonin; C042390:alpha-methylserotonin; D012701:Serotonin; D018738:Hexamethonium; D017294:Ondansetron; D000077526:Tropisetron; C045918:2-methyl-5-HT; C055971:zacopride; C032663:LY 53857