Calcium mobilization and phosphatidylinositol turnover in vas deferens smooth muscle of diabetic rats

Abstract

The study concerned Ca 2+ channels that are receptor-operated by norepinephrine (NE) and mediate hyper-reactivity of vas deferens smooth muscle from rats with streptozotocin (STZ)-induced diabetes, and the mediatory responses of these channels, such as tension development, Ca 2+ uptake and phosphatidylinositol (PI) turnover. The contractile responses induced by adrenoceptor agonists were significantly greater in diabetic rat vas deferens than in the controls. A greater Ca 2+ uptake was induced by 10 −5 M NE in strips from diabetic rats than in the controls. The uptake of Ca 2+ was completely inhibited by 10 −6 M prazosin but not by 10 −5 M verapamil. Enhancement of Ca 2+ release by 10 −5 M NE was faster and greater in diabetic muscles than in the controls. The accumulation of [ 3H]inositol phosphates was increased 4-fold in the controls and 7-fold in diabetic muscles by 10 −5 M NE. This increase was completely inhibited by 10 −6 M prazosin but not by 10 −6 M yohimbine. The data suggest that vas deferens smooth muscle hyper-reactivity in diabetic rats is due to increased PI turnover mediated by α 1-adrenoceptors, to the release of intracellular bound Ca 2+ and to an increase of Ca 2+ uptake through receptor-operated Ca 2+ channels.