α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture (original) (raw)

Abstract

Madin—Darby canine kidney cells (MDCK) synthesize prostaglandin (PG) F2α, PGI2 (measured as 6-keto-PGE1α), PGE2, PGD2, and thromboxane A2 (measured as thromboxane B2). When incubated in the presence of norepinephrine (6 μM), the syntheses of these arachidonic acid metabolites are stimulated 3-fold. Norepinephrine's effect can be antagonized by the addition of α-adrenergic receptor blocking agents (phenoxybenzamine>phentolamine>yohimbine>dibenamine>tolazoline) but not by the β-adrenergic blocking drug propranolol. Norepinephrine's stimulation is also inhibited by low concentrations of dihydroergotamine, bromocryptine, ergocryptine, and ergotamine. The stimulation of PG synthesis by norepinephrine is reversible, continues during the 24 hr 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. Neither phenoxybenzamine nor ergotamine at concentrations that block norepinephrine's stimulation of PG biosynthesis suppresses the increase in PG synthesis induced by exogenous arachidonic acid, suggesting that the α-adrenergic regulation is not occurring primarily at the cyclooxygenase step in the metabolism of arachidonic acid. In mouse 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. Taken together, these results suggest that α-adrenergic receptor stimulation promotes the deacylation of phospholipids by MDCK cells whereas β-adrenergic mechanisms lead to activation of similar pathways in WEHI-5 cells.

Keywords: phospholipase A2, prostaglandins, adrenergic antagonists, norepinephrine, adrenergic receptors

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Selected References

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