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5‐Hydroxytryptamine‐induced bronchoconstriction in the guinea‐pig: effect of 5‐HT 2 receptor activation on acetylcholine release
Author(s) -
MacquinMavier Isabelle,
Jarreau PierreHenri,
Istin Nathalie,
Harf Alain
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12291.x
Subject(s) - hexamethonium , bronchoconstriction , atropine , ketanserin , vagotomy , muscarinic acetylcholine receptor , endocrinology , guinea pig , chemistry , medicine , acetylcholine , 5 ht receptor , pharmacology , serotonin , receptor , asthma
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‐HT 3 antagonist ICS 205–930, or either 0.01 or 0.1 mg kg −1 of the 5‐HT 2 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‐HT 2 receptors in these responses, we studied the effects in vagotomized guinea‐pigs of atropine on the bronchoconstriction induced by the 5‐HT 2 agonist, α‐methyl‐5‐HT, infused at rates of 40 and 80 ng kg −1 s −1 . At both rates, atropine significantly reduced the bronchoconstrictor responses to α‐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‐HT 2 receptors which are probably located on the postganglionic parasympathetic nerve endings.