Norepinephrine stimulation of adenylate cyclase potentiates protein kinase C action: electrophysiological studies in the dentate gyrus.
Protein kinase C and norepinephrine-stimulated adenylate cyclase have been linked to formation of long-term potentiation in the dentate gyrus. However, little is known about second messenger system interactions regulating synaptic transmission. In electrophysiological studies of the dentate gyrus, we observe synergistic interactions between norepinephrine and phorbol esters, activators of protein kinase C. Norepinephrine markedly potentiates the block of adenosine's inhibitory action by phorbol esters. Norepinephrine's action is mimicked by the beta-adrenoceptor agonist isoproterenol and blocked by the beta-adrenoceptor antagonists timolol and propranolol. Forskolin also mimicks norepinephrine's action. Accordingly, norepinephrine's potentiation of protein kinase C appears to be mediated by the cyclic AMP second messenger system. This mechanism may contribute to norepinephrine's facilitation of long-term potentiation in the dentate gyrus.
Stratton
K R
KR
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Baraban
J M
JM
Worley
P F
PF
D000262:Adenylyl Cyclases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects*
D010703:Phorbol Esters; D011943:Receptors, Adrenergic, beta; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine