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

α-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 α-methyl-5-HT induced biphasic responses (contraction followed by relaxation) in guinea pig tracheal rings. The relaxing phase caused by 32 μM α-methyl-5-HT was blocked by 0.1 μM propranolol. Furthermore, during an ongoing histamine-induced contraction, α-methyl-5-HT (0.1–100 μM) produced a concentration-dependent relaxation starting at 10 μM. This relaxation was fully abolished by 0.1 μM propranolol or 1 μM ICI 118,551 (a selective β2-adrenoceptor antagonist). Additionally, in electrophysiological recordings, 32 μM α-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 μM salbutamol. Thus, we concluded that α-methyl-5-HT activates β2-adrenoceptors in guinea pig tracheal smooth muscle at concentrations ≥10 μM. This effect must be taken into account when this drug is used in airway smooth muscle and in other tissues expressing β2-adrenoceptors.