Different mode of action between norepinephrine and phenylephrine on prostaglandin synthesis by dog renal inner medullary slices.

Abstract

Abstract-The dog renal inner medullary slices synthesized and released prostaglandin (PG) E2, PGF21, PGI2 (measured as 6-keto-PGF,.) and thromboxane (TX) A2 (measured as TXB2). When incubated in the presence of norepinephrine, the synthesis of these arachidonic acid metabolites were stimulated about 2-fold. The norepinephrine effect could be antagonized by the addition of an a-adrenoceptor blocking agent, phenoxy benzamine, but not by a Q-adrenoceptor blocking drug, propranolol. Phenoxybenzamine at concentrations that block norepinephrine stimulation of prostaglandin biosynthesis did not suppress the increase in prostaglandins synthesized by exogenous arachidonic acid. By contrast, phenylephrine caused only PGI2 production without producing other prostaglandins and thromboxane. This phenylephrine effect could not be antagonized by either a or 8-adrenoceptor blocking agents, but it was abolished by the specific PGI2 synthetase inhibitors 15-hydroperoxy arachidonic acid and tranylcypromine. These results suggest that norepinephrine-induced prostaglandin synthesis is mediated via an a-adrenergic receptor mechanism, whereas phenylephrine stimulation is primarily occurring at the step which follows the cyclooxygenase reaction in the metabolism of arachidonic acid.