α-methyl-5-HT, a 5-HT2 receptor agonist, stimulates β2-adrenoceptors in guinea pig airway smooth muscle

alpha-Methyl-5-HT is widely used as a high-affinity 5-HT2 receptors agonist, though some studies have postulated that this drug also activates other serotonergic receptors. In the present work, we found that a wide range of concentrations of alpha-methyl-5-HT induced biphasic responses (contraction followed by relaxation) in guinea pig tracheal rings. The relaxing phase caused by 32 mu M alpha-methyl-5-HT was blocked by 0.1 mu M propranolol. Furthermore, during an ongoing histamine-induced contraction, alpha-methyl-5-HT (0.1-100 mu M) produced a concentration-dependent relaxation starting at 10 mu M. This relaxation was fully abolished by 0.1 mu M propranolol or 1 mu M ICI 118,551 (a selective beta(2)-adrenoceptor antagonist). Additionally, in electrophysiological recordings, 32 mu M alpha-methyl-5-HT also enhanced the membrane K+ currents of single tracheal myocytes, an effect reverted by propranolol and ICI 118,551, and mimicked by 0.1 mu M salbutamol. Thus, we concluded that alpha-methyl-5-HT activates beta(2)-adrenoceptors in guinea pig tracheal smooth muscle at concentrations >= 10 mu M. This effect must be taken into account when this drug is used in airway smooth muscle and in other tissues expressing beta(2)-adrenoceptors. (c) 2006 Elsevier Ltd. All rights reserved.