THE RELATIONSHIP BETWEEN PHOSPHATIDYLINOSITOL METABOLISM AND MOBILIZATION OF INTRACELLULAR CALCIUM ELICITED BY ALPHA1-ADRENERGIC RECEPTOR STIMULATION IN BC3H-1 MUSCLE-CELLS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 26  (3) , 405-413
Abstract
The BC3H-1 cell is a stable cell line of probable smooth muscle origin which expresses nicotinic acetylcholine, .alpha.1- and .beta.2-adrenergic receptors on its cell surface. Stimulation of the .alpha.1 receptor mobilizes 70% of the intracellular Ca2+ within a 2- to 3-min interval. To delineate further the linkage between .alpha.1-receptor occupation and response, the quantitative relationship between fractional occupation of the receptor, the turnover of inositol-containing phospholipids and the Ca2+ efflux was examined. .alpha.1-Receptor activation stimulates the incorporation of [3H]inositol into phosphatidylinositol and the enhanced incorporation is linear over a 60-min interval. Agonist-elicited increases in hydrolysis of phosphatidylinositol and phosphatidylinositol mono- and bisphosphate develop more slowly, and a 5-min lag in enhanced formation of inositol trisphosphate, inositol bisphosphate, and inositol monophosphate is evident. The increased rate of Ca2+ efflux and enhanced rate of inositol incorporation into phosphatidylinositol elicited by phenylephrine exhibit virtually identical dependencies on agonist concentrations. Fractional inactivation of receptors with phenoxybenzamine shows equivalent increments in the reduction of the 2 intracellular responses. Both responses are linearly related to the residual receptor sites remaining after fractional inactivation. These findings indicate an absence of a receptor reserve in activating these intracellular events. Athough .alpha. receptor occupation stimulates phosphatidylinositol hydrolysis, no evidence is provided that this event would precede Ca2+ release. Should inositol trisphosphate mediate intracellar Ca2+ mobilization in these cells, it would be active in extremely low concentrations or occur as a tightly coupled event in a microscopic environment.