Effect of a novel 5-hydroxytryptamine3-antagonist, GR38032F, on the 5-hydroxytryptamine-induced increase in carotid sinus nerve activity in rats.

The mass discharges of the carotid sinus nerve were recorded and the effect of 5-hydroxytryptamine3 (5-HT3) antagonist on the 5-HT-induced alteration of the carotid sinus nerve activity was studied in anesthetized rats. The i.v. bolus injection of 5-HT produced a rapid and dose-dependent increase in the carotid sinus nerve activity. Pretreatment with a selective 5-HT3 antagonist, GR38032F (3 x 10(-8) mol/kg), caused a parallel shift to the right in the dose-response curve. A selective 5-HT3 agonist, 2-methyl-5-HT, also produced a dose-dependent increase in the carotid sinus nerve activity. GR38032F (3 x 10(-9) and 3 x 10(-8) mol/kg) pretreatment caused a parallel rightward shift in the dose-response curves. Neither methysergide (3 x 10(-7) mol/kg), which possesses both 5-HT1-like partial agonistic and 5-HT2 antagonistic actions, nor ketanserin (3 x 10(-7) mol/kg), a selective 5-HT2 antagonist, affected the 5-HT-induced increase in carotid sinus nerve activity. GR38032F (3 x 10(-8) mol/kg) produced no significant change in the NaCN (1 mg/kg)-induced increase in carotid sinus nerve activity. These findings indicate that the 5-HT-induced increase in carotid sinus nerve activity is mediated by the 5-HT3 receptor mechanism in the carotid body of the rat.