Potentiation of cAMP responses by metabotropic glutamate receptors depresses excitatory synaptic transmission by a kinase-independent mechanism

Neuron. 1994 May;12(5):1121-9. doi: 10.1016/0896-6273(94)90319-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology
  • Analysis of Variance
  • Animals
  • Cyclic AMP / pharmacology*
  • Cyclic AMP / physiology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Electric Stimulation
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology*
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Models, Neurological
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurotoxins / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology*
  • Staurosporine
  • Synapses / drug effects
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Alkaloids
  • Neurotoxins
  • Receptors, Adrenergic, beta
  • Receptors, Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Staurosporine
  • Isoproterenol