Effect of a selective β 2-adrenoceptor agonist, procaterol, on tissue cyclic AMP level : Its determination after tissue fixation by microwave irradiation

Abstract

Intravenous injection of procaterol (1μmole/kg of body wt). a selective β 2-agonist, into conscious rats caused increases in tissue cyclic AMP, with a peak level at 2 min after injection. Two- to 3-fbld increases were induced by procaterol in heart and liver, while 6- to 10-fold increases were induced in trachea, lung and skeletal muscle. Procaterol-induced alterations in cyclic AMP levels in trachea and skeletal muscle were characterized by their long duration (over 2 hr). The duration of the procaterol action reflected sustained stimulation of β-adrenoceptor-linked adenylate cyclase, because the tissue level of cyclic AMP subsided rapidly to the base-line level when propranolol (10 μmoles/kg) was injected intravenously immediately after the peak level was obtained with procaterol. 3-Isobutyl- 1-methylxanthine (50 μmoles/kg, s.c.), an inhibitor of phosphodiesterase, was very effective in enhancing the procaterol-induced increases in cyclic AMP in trachea, lung and skeletal muscle. Procaterol caused increases in tissue cyclic AMP levels in skeletal muscle. trachea, lung and heart at doses of 1, 10, 10 and 100 nmoles/kg, respectively, in a dose-dependent manner. It was concluded that procaterol was a long-acting and selective β 2-agonist which was effective in increasing tissue cyclic AMP, as well as in increasing bronchodilator and metabolic alterations. Determination of tissue cyclic AMP using rapid tissue fixation by microwave irradiation could serve as a useful means in vivo for the interaction of β-agonists or antagonists with β 1- or β 2-adrenoceptors.