Pharmacological identification of the alpha-adrenergic receptor type which inhibits the beta-adrenergic activated adenylate cyclase system in cultured astrocytes.
The adrenergic agonist norepinephrine can exert its influence on cell function by activating both alpha- and beta-adrenergic receptors. In astrocytes, the alpha-adrenergic receptor activity of norepinephrine is known to inhibit the cyclic AMP response elicited by its action at beta-adrenergic receptors. Pharmacological studies were conducted to identify the subtype of alpha-adrenergic receptor which mediates this inhibitory action. The alpha 2-adrenergic antagonist yohimbine potentiated the cyclic AMP response elicited by norepinephrine, whereas the alpha 1-adrenergic antagonist prazosin did not affect the response. The alpha 2-adrenergic agonist clonidine inhibited the cyclic AMP response elicited by the beta-adrenergic agonist isoproterenol and this inhibition could be blocked by yohimbine but not by prazosin. In contrast, the alpha 1-adrenergic agonist phenylephrine did not inhibit the cyclic AMP response to isoproterenol. These studies indicate that the inhibitory action of norepinephrine is mediated by its action at alpha 2-adrenergic receptors.
Northam
W J
WJ
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284.
Bedoy
C A
CA
Mobley
P L
PL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D004789:Enzyme Activation; D007545:Isoproterenol / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D011224:Prazosin