Characteristics of Acetylcholine-Induced Phosphorylase a Activity in Uterine Segments as a Substitute for Contractile Response to Acetylcholine

Abstract

Studies were made on whether the ACh-induced phosphorylase a activity in isolated rat uterine muscle segments could be used as a substitute for the contractile response to ACh. This ACh-induced phosphorylase a activity was dependent upon the concentration of ACh and was inhibited by atropine, suggesting that it was linked to muscarinic ACh receptors. Both extracellular calcium and an increase of the intracellular calcium concentration were needed for its activation by ACh. Ca2+-antagonists such as Co2+, diltiazem, nitrendipine and verapamil inhibited the ACh-induced activity, suggesting that the activation by ACh required the influx of calcium ions into the uterine muscle through Ca2+-antagonist sensitive Ca2+ channels. The IC50 values of CoCI2, diltiazem, nitrendipine and verapamil on the ACh-induced phosphorylase a activity were 3.4 × 10−3 M, 2.5 × 10−4 M, 2.5 × 10−5 M and 1.1 × 10−4 M, respectively. These values were comparable with the IC50 values of these Ca2+-antagonists on the contractile response of isolated rat uterine muscle segments to 3 × 10−4 M ACh. The inhibitory effects of Co2+, nitrendipine and verapamil, but not diltiazem, on ACh-induced phosphorylase a activity were attenuated by higher concentrations of CaCI2 (0.36 to 2 mM). These findings suggested that the ACh-induced phosphorylase a activity in isolated rat uterine muscle segments could be used as a substitute for the contractile response to ACh.