Regulation of cyclic AMP formation in brain tissue by alpha-adrenergic receptors: requisite intermediacy of prostaglandins of the E series.
The accumulations of cyclic AMP elicited by norepinephrine in slices of rat cerebral cortex or hypothalamus were markedly reduced after incubations with prostaglandin synthetase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1) inhibitors such as indomethacin, aspirin, flufenamic acid, and acetoaminophen. Responses of cyclic AMP-generating systems to beta-adrenergic agonists or adenosine were unchanged by treatment with indomethacin and the reduction in the norepinephrine response appeared due primarily to a loss of the alpha-adrenergic component. The accumulation of cyclic AMP elicited by prostaglandin E2 [mean effective dose (EC50) 4 micro M] was increased by 2-fold by treatment with indomethacin. The alpha-adrenergic component of the norepinephrine response was fully restored by very low concentrations of prostaglandin E2 (EC50 20 nM). Prostaglandins of the F series had no effect on cyclic AMP generation under a variety of conditions. It appears that low levels of prostaglandins of the E series are required--perhaps by a calcium-dependent mechanism--for the expression of alpha-adrenergic receptor-mediated activation of cyclic AMP formation in brain tissue.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; D009638:Norepinephrine; D007213:Indomethacin