Inhibition of Cyclic AMP Formation by a Selective Metabotropic Glutamate Receptor Agonist

Inhibition of Cyclic AMP Formation by a Selective Metabotropic Glutamate Receptor Agonist Abstract: It is well documented that the effects of excitatory ammo acid (EAA) agonists on phosphoinositide hydrolysis involve a GTP‐binding protein‐linked or “metabotropic’ receptor mechanism. The mechanisms by which EAAs alter cyclic AMP levels in brain slices, however, are not yet clear. In this study, the selective metabotropic EAA agonist trans‐(±)‐l‐aminocyclopentane‐l,3‐dicarboxylic acid and its isomers were examined for effects on basal and forskolin‐stimulated cyclic AMP formation in slices of the rat hippocampus. Trans‐(±)‐l‐Aminocyclopentane‐l,3‐dicarboxylic acid had little effect on basal cyclic AMP but inhibited forskolin‐stimulated cyclic AMP formation in a biphasic manner. The 1S,3R isomer of 1‐aminocy‐clopentane‐l,3‐dicarboxylic acid produced potent but only partial (~50%) inhibition of forskolin‐stimulated cyclic AMP formation. 1R,3S–l‐Aminocyclopentane‐l,3‐dicarboxylic acid fully inhibited forskolin‐stimulated cyclic AMP but with lower potency than the IS,3R isomer. These results show that in addition to the formation of phosphoinositide‐derived second messengers, the cellular consequences of selectively activating hippocampal metabotropic EAA receptors include an alteration of cellular cyclic AMP levels. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Inhibition of Cyclic AMP Formation by a Selective Metabotropic Glutamate Receptor Agonist

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Publisher
Wiley
Copyright
Copyright © 1992 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1992.tb09381.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: It is well documented that the effects of excitatory ammo acid (EAA) agonists on phosphoinositide hydrolysis involve a GTP‐binding protein‐linked or “metabotropic’ receptor mechanism. The mechanisms by which EAAs alter cyclic AMP levels in brain slices, however, are not yet clear. In this study, the selective metabotropic EAA agonist trans‐(±)‐l‐aminocyclopentane‐l,3‐dicarboxylic acid and its isomers were examined for effects on basal and forskolin‐stimulated cyclic AMP formation in slices of the rat hippocampus. Trans‐(±)‐l‐Aminocyclopentane‐l,3‐dicarboxylic acid had little effect on basal cyclic AMP but inhibited forskolin‐stimulated cyclic AMP formation in a biphasic manner. The 1S,3R isomer of 1‐aminocy‐clopentane‐l,3‐dicarboxylic acid produced potent but only partial (~50%) inhibition of forskolin‐stimulated cyclic AMP formation. 1R,3S–l‐Aminocyclopentane‐l,3‐dicarboxylic acid fully inhibited forskolin‐stimulated cyclic AMP but with lower potency than the IS,3R isomer. These results show that in addition to the formation of phosphoinositide‐derived second messengers, the cellular consequences of selectively activating hippocampal metabotropic EAA receptors include an alteration of cellular cyclic AMP levels.

Journal

Journal of NeurochemistryWiley

Published: Mar 1, 1992

References

  • Excitatory effects of ACPD receptor activation in the hippocampus are mediated by direct effects on pyramidal cells and blockade of synaptic inhibition
    Desai, Desai; Conn, Conn
  • Modulation of VIP‐stimulated cAMP formation by excitatory amino acids in mouse cerebral cortex
    Schaad, Schaad; Schorderet, Schorderet; Magistretti, Magistretti

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