α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture

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Abstract
Madin-Darby canine kidney cells (MDCK non-neoplastic) synthesize prostaglandin (PG)F2.alpha., PGI2 (measured as 6-keto-PGE1.alpha.), PGE2, PGD2 and thromboxane A2 (measured as thromboxane B2). When incubated in the presence of norepinephrine (6 .mu.M), the syntheses of these arachidonic acid metabolites are stimulated 3-fold. Norepinephrine''s effect can be antagonized by the addition of .alpha.-adrenergic receptor blocking agents (phenoxybenzamine > phentolamine > yohimbine > dibenamine > tolazoline) but not by the .beta.-adrenergic blocking drug propranolol. Norepinephrine''s stimulation is inhibited by low concentrations of dihydroergotamine, bromocryptine, ergocryptine and ergotamine. The stimulation of PG synthesis by norepinephrine is reversible, continues during the 24 h of incubation, and requires the presence of norepinephrine at the receptor site, but it is not blocked by the addition of colchicine, cytochalasin B or cycloheximide. Phenoxybenzamine or ergotamine at concentrations that block norepinephrine''s stimulation of PG biosynthesis did not suppress the increase in PG synthesis induced by exogenous arachidonic acid; apparently the .alpha.-adrenergic regulation is not occurring primarily at the cyclooxygenase step in the metabolism of arachidonic acid. In mouse neoplastic lymphoma cells (WEHI-5), low concentrations of isoproterenol or norepinephrine stimulate the synthesis of thromboxane, an effect that can be blocked by the addition of propranolol but not by relatively high concentrations of phenoxybenzamine or ergotamine. .alpha.-Adrenergic receptor stimulation apparently promotes the deacylation of phospholipids by MDCK cells whereas .beta.-adrenergic mechanisms lead to activation of similar pathways in WEHI-5 cells.

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