Alpha-methyl-5-HT, a 5-HT2 receptor agonist, stimulates beta2-adrenoceptors in guinea pig airway smooth muscle.
Alpha-methyl-5-HT is widely used as a high-affinity 5-HT(2) 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 32microM alpha-methyl-5-HT was blocked by 0.1microM propranolol. Furthermore, during an ongoing histamine-induced contraction, alpha-methyl-5-HT (0.1-100microM) produced a concentration-dependent relaxation starting at 10microM. This relaxation was fully abolished by 0.1microM propranolol or 1microM ICI 118,551 (a selective beta(2)-adrenoceptor antagonist). Additionally, in electrophysiological recordings, 32microM 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 0.1microM salbutamol. Thus, we concluded that alpha-methyl-5-HT activates beta(2)-adrenoceptors in guinea pig tracheal smooth muscle at concentrations >or=10microM. This effect must be taken into account when this drug is used in airway smooth muscle and in other tissues expressing beta(2)-adrenoceptors.
Campos-Bedolla
Patricia
P
Unidad de Investigación Médica en Enfermedades Neurológicas, Instituto Mexicano del Seguro Social, México DF, Mexico.
Vargas
Mario H
MH
Calixto
Eduardo
E
Segura
Patricia
P
Mendoza-Patiño
Nicandro
N
Figueroa
Alejandra
A
Flores-Soto
Edgar
E
Barajas-López
Carlos
C
Montaño
Luis M
LM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D010726:Phosphodiesterase Inhibitors; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D002110:Caffeine; C026777:ICI 118551; D007650:Ketanserin; D011433:Propranolol; D002118:Calcium