Effects of fenoterol on β-adrenoceptor and muscarinic M2 receptor function in bovine tracheal smooth muscle

• Published in: European journal of pharmacology 2001-05, Vol.419 (2-3), p.253-259
• Main Authors: DE VRIES, Berber, ROFFEL, Ad F, KOOISTRA, Jolanda M, MEURS, Herman, ZAAGSMA, Johan
• Format: Article
• Language: English
• Subjects: Adenylate Cyclase Toxin; Adenylyl Cyclases - metabolism; Adrenergic beta-Agonists - pharmacology; Animals; Biological and medical sciences; Cattle; Drug Interactions; Fenoterol - pharmacology; Medical sciences; Methacholine Chloride - pharmacology; Muscarinic Agonists - pharmacology; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - enzymology; Pertussis Toxin; Pharmacology. Drug treatments; Receptor, Muscarinic M2; Receptors, Adrenergic, beta - drug effects; Receptors, Muscarinic - drug effects; Respiratory system; Trachea; Virulence Factors, Bordetella - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)00978-5

Prolonged (18 h) incubation of isolated bovine tracheal smooth muscle with the beta2-adrenoceptor agonist fenoterol (10 microM) induced desensitization of isoprenaline-induced adenylyl cyclase activity in bovine tracheal smooth muscle membranes, characterized by a 25% decrease in maximal effect (Emax) (P < 0.05), while the sensitivity to the agonist (pEC50) was unchanged. The Emax value of isoprenaline-induced smooth muscle relaxation of submaximal methacholine-induced contractile tones was similarly reduced by about 25% (P < 0.001), while the pEC50 value was diminished by 1.0 log unit (P < 0.001). As determined by 30 microM gallamine-induced muscarinic M2 receptor antagonism and pertussis toxin-induced inactivation of G(i alpha), muscarinic M2 receptor-mediated functional antagonism did not play a role in isoprenaline-induced relaxation of bovine tracheal smooth muscle contracted by methacholine, both in control and in 18-h fenoterol-treated tissue. In line with these observations, we found no enhanced muscarinic M2 receptor-mediated inhibition of 1 microM forskolin-stimulated adenylyl cyclase activity after 18-h fenoterol treatment. These data indicate that 18-h fenoterol treatment of bovine tracheal smooth muscle induces beta2-adrenoceptor desensitization and reduced functional antagonism of methacholine-induced contraction by beta-adrenoceptor agonists, without a change of muscarinic M2 receptor function.