Phorbol ester-stimulated 6-keto-prostaglandin F1 alpha in aortas from control and aldosterone-salt rats.

OBJECTIVE

To assess the contribution of protein kinase C to the production of 6-keto-prostaglandin F1 alpha by stimulating protein kinase C directly.

RESULTS

Phorbol myristate acetate caused a time-dependent increase in 6-keto-prostaglandin F1 alpha and thromboxane B2. The time course was slower than for norepinephrine-stimulated production of these metabolites, but the pattern was similar, with thromboxane B2 appearing before 6-keto-prostaglandin F1 alpha. The phorbol myristate acetate concentration-response curves for 6-keto-prostaglandin F1 alpha production for control-salt and aldosterone-salt hypertensive rats were equivalent. Staurosporine inhibited phorbol myristate acetate-stimulated 6-keto-prostaglandin F1 alpha production in control-salt and aldosterone-salt hypertensive rats concentration-dependently. The staurosporine median inhibitory concentration for phorbol myristate acetate-stimulated 6-keto-prostaglandin F1 alpha production was twofold greater in aldosterone-salt hypertensive than in control-salt rats, but was similar for norepinephrine-stimulated 6-keto-prostaglandin F1 alpha.

CONCLUSION

Activation of protein kinase C results in increases in arachidonic acid metabolites, but alterations in this pathway do not seem to be responsible for the differences observed with norepinephrine-stimulated 6-keto-prostaglandin F1 alpha production. The present data offer some support for the concept of direct coupling between the alpha 1-adrenoceptor and phospholipase A2.