Relationship between phosphatidylinositol turnover and Ca++ mobilization induced by alpha-1 adrenoceptor stimulation in the rat aorta.
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.
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine