Potentiation of cAMP responses by metabotropic glutamate receptors depresses excitatory synaptic transmission by a kinase-independent mechanism.
Coactivation of metabotropic glutamate receptors (mGluRs) and beta-adrenergic receptors causes a synergistic increase in cAMP formation in the rat hippocampus. Increases in cAMP are known to have many actions in the hippocampus via activation of cAMP-dependent protein kinase. We now report that coactivation of mGluRs and beta-adrenergic receptors induces an acute depression of EPSCs at the Schaffer collateral-CA1 synapse. Interestingly, this depression of EPSCs is dependent upon increases in cAMP levels but independent of protein kinase activity. A series of studies suggests that cAMP-mediated depression of EPSCs is dependent on metabolism of cAMP and release of adenosine or 5'-AMP into the extracellular space with resultant activation of presynaptic adenosine receptors. These studies suggest that cAMP can have local hormone-like effects in the hippocampal formation which are independent of cAMP-dependent protein kinase.
Gereau
R W
RW
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Conn
P J
PJ
D000470:Alkaloids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology* / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000470:Alkaloids; D009498:Neurotoxins; D011943:Receptors, Adrenergic, beta; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D007545:Isoproterenol