Chiu A T, Bozarth J M, Timmermans P B
J Pharmacol Exp Ther. 1987 Jan;240(1):123-7.
In this study the causal relationship between alpha-1 adrenoceptor activation mediating contraction in rat aorta and the mediatory responses, such as phosphatidylinositol turnover and intracellular Ca++ release has been evaluated. Norepinephrine (1 X 10(-5) M) increased maximally the accumulation of [3H]inositol-1-PO4. In the presence of LiCl (10 mM) the norepinephrine-induced accumulation of [3H]inositol-1-PO4 occurred in a time-dependent, linear fashion (0-60 min), achieving a 13-fold increase over the unstimulated control at 60 min of exposure. This stimulation could be inhibited by prazosin (1 X 10(-7) M) but not by yohimbine (1 X 10(-7) M), whereas it was also unaffected by nifedipine (3 X 10(-7) M). Potassium depolarization did not invoke [3H]inositol-1-PO4 production nor did Sgd 101/75 in concentrations of up to 3 X 10(-5) M, although both have been found effective in stimulating a large influx of Ca++ for their contraction. However, the effect of norepinephrine on the formation of [3H] inositol-1-PO4 was antagonized by Sgd 101/75. A positive correlation (correlation coefficient 0.966) between intracellular Ca++ release and phosphatidylinositol turnover induced by a series of alpha-1 adrenoceptor agonists was demonstrated. These data support the hypothesis that stimulation of alpha-1 adrenoceptors in rat aorta can elicit two distinct processes of Ca++ utilization for contraction. One facilitates exclusively an influx of extracellular Ca++ which is independent of phosphatidylinositol turnover, whereas the other activates the release of intracellularly bound Ca++ that may be mediated primarily by phosphatidylinositol metabolism.
