5-Hydroxytryptamine-induced bronchoconstriction in the guinea-pig: effect of 5-HT2 receptor activation on acetylcholine release.

1. The bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were studied in the guinea-pig to establish whether they are partly attributable to parasympathetic activation within the airways. 5-HT dose-response curves were constructed in anaesthetized and ventilated guinea-pigs pretreated with saline, or by bilateral cervical vagotomy or vagotomy plus atropine 3 mg kg-1, i.v. Vagotomy had no effect on 5-HT-induced bronchoconstriction but vagotomy plus atropine significantly reduced it. 2. To determine whether parasympathetic activation within the airways resulted from pre- or postganglionic stimulation, 5-HT dose-response curves were constructed for two groups of vagotomized guinea-pigs treated with hexamethonium 2 mg kg-1, or hexamethonium 2 mg kg-1, plus atropine 3 mg kg-1. Guinea-pigs treated with hexamethonium plus atropine experienced significantly less 5-HT-induced bronchoconstriction than those treated with hexamethonium alone. 3. To characterize the subtype of 5-HT receptors involved in the activation of the parasympathetic system by 5-HT, dose-response curves to 5-HT were constructed for four groups of vagotomized guinea-pigs treated with saline, 1 mg kg-1 of the 5-HT3 antagonist ICS 205-930, or either 0.01 or 0.1 mg kg-1 of the 5-HT2 antagonist ketanserin. ICS 205-930 enhanced 5-HT-induced bronchoconstriction but 0.01 mg kg-1 ketanserin inhibited it significantly and 0.1 mg kg-1 ketanserin abolished it. To confirm the involvement of 5-HT2 receptors in these responses, we studied the effects in vagotomized guinea-pigs of atropine on the bronchoconstriction induced by the 5-HT2 agonist,x alpha-methyl-5-HT, infused at rates of 40 and 80ngkg-1s-'. At both rates, atropine significantly reduced the bronchoconstrictor responses to alpha-methyl-5-HT. 4. The above results indicate that 5-HT-induced bronchoconstriction is indeed partly mediated by parasympathetic activation within the airways. This activation is mediated by stimulation of 5-HT2 receptors which are probably located on the postganglionic parasympathetic nerve endings.