Prolonged (18 h) incubation of isolated bovine tracheal smooth muscle with the beta (2)-adrenoceptor agonist fenoterol (10 muM) induced desensitization of isoprenaline-induced adenylyl cyclase activity in bovine tracheal smooth muscle membranes, characterized by a 25% decrease in maximal effect (E-max) (P <0.05), while the sensitivity to the agonist (pEC(50)) was unchanged. The E-max value of isoprenaline-induced smooth muscle relaxation of submaximal methacholine-induced contractile tones was similarly reduced by about 25% (P <0.001), while the pEC(50) value was diminished by 1.0 log unit (P <0.001). As determined by 30 M gallamine-induced muscarinic M-2 receptor antagonism and pertussis toxin-induced inactivation of G(1 alpha) muscarinic M-2 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 M-2 receptor-mediated inhibition of I muM forskolin-stimulated adenylyl cyclase activity after 18-h fenoterol treatment. These data indicate that 18-h fenoterol treatment of bovine tracheal smooth muscle induces beta (2)-adrenoceptor desensitization and reduced functional antagonism of methacholine-induced contraction by beta -adrenoceptor agonists, without a change of muscarinic M-2 receptor function. (C) 2001 Published by Elsevier Science B.V.
|Tijdschrift||European Journal of Pharmacology|
|Nummer van het tijdschrift||2-3|
|Status||Published - 11-mei-2001|