Relaxing actions of procaterol, a beta 2-adrenoceptor stimulant, on smooth muscle cells of the dog trachea

Abstract

1. The effects of procaterol, a beta 2-adrenoceptor agonist, on smooth muscle cells of the dog trachea were investigated by use of microelectrode and isometric tension recording methods, and by measurement of Ca transients as estimated from the fura-2 fluorescence, adenosine 3':5'-cyclic monophosphate (cyclic AMP) and breakdown of phosphatidylinositols. 2. Procaterol hyperpolarized the membrane and increased the ionic conductance (above 10 nM) in a dose-dependent manner. These actions were inhibited by propranolol. 3. Procaterol inhibited the mechanical responses evoked by acetylcholine (ACh), histamine or 5-hydroxytryptamine (5-HT), in the presence or absence of Ca2+ in the bath solution, but not that evoked by high concentrations of ACh (1 microM). The ID50 value of procaterol for the peak amplitude of the ACh-induced contraction (30 nM) was 0.3 nM. The equivalent values for the histamine-induced phasic and tonic responses (10 microM) were 0.15 and 0.01 nM), respectively. 4. Procaterol (over 1 nM) increased the amount of cyclic AMP in a dose-dependent manner which was blocked by prior application of propranolol. 5. Procaterol did not alter the changes in the amounts of phosphatidylinositol 4,5-bisphosphate (PI-P2) and phosphatidic acid (PA) induced by ACh, histamine or 5-HT. Thus, the synthesis of inositol 1,4,5-trisphosphate is not affected by stimulation of the beta 2-adrenoceptor. 6. ACh increased the free Ca2+ concentration to a greater extent than that produced by histamine or 5-HT. These changes were reduced by procaterol, except for those induced by high concentrations of ACh (over 1 microM). 7. It is concluded that procaterol relaxes tissues precontracted by various agonists due to a reduction in the free Ca2+. This inhibitory action may be due to an increase in the amount of cyclic AMP but does not result from an inhibition of the hydrolysis of phosphatidyl inositols. The hyperpolarization induced by procaterol may partly contribute to the observed relaxation.