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Metabotropic Glutamate Receptor (mGluR)‐Mediated Potentiation of Cyclic AMP Responses Does Not Require Phosphoinositide Hydrolysis: Mediation by a Group II‐Like mGluR
Author(s) -
Winder Danny G.,
Conn P. Jeffrey
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64020592.x
Subject(s) - metabotropic glutamate receptor , long term potentiation , agonist , metabotropic receptor , chemistry , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 7 , acpd , neuroscience , biology , pharmacology , biochemistry , receptor
Metabotropic glutamate receptors (mGluRs) in the CNS are coupled to a variety of second messenger systems, the best characterized of which is activation of phosphoinositide hydrolysis. Recently, we found that activation of mGluRs in rat brain slices by the selective mGluR agonist 1‐aminocyclopentane‐1 S ,3 R ‐dicarboxylic acid (1 S ,3 R ‐ACPD) potentiates cyclic AMP (cAMP) responses elicited by activation of other receptors coupled to G s . It has been suggested that mGluR‐mediated potentiation of cAMP responses is secondary to activation of phosphoinositide hydrolysis. However, preliminary evidence suggests that this is not the case. Therefore, we designed a series of experiments to test more fully the hypothesis that mGluR‐mediated potentiation of cAMP responses is secondary to phosphoinositide hydrolysis. Inhibitors of both protein kinase C and intracellular calcium mobilization failed to antagonize 1 S ,3 R ‐ACPD‐stimulated potentiation of cAMP responses. Further, coapplication of phorbol esters and 1 S ,3 R ‐ACPD induced a cAMP response that was greater than additive. Finally, ( RS )‐3,5‐dihydroxyphenylglycine, a selective agonist of mGluRs coupled to phosphoinositide hydrolysis, failed to potentiate cAMP responses, whereas (2 S ,1′ R ,2′ R ,3′ R )‐2‐(2,3‐dicarboxycyclopropyl)glycine, an mGluR agonist that does not activate mGluRs coupled to phosphoinositide hydrolysis, elicited a robust potentiation of cAMP responses. In total, these data strongly suggest that mGluR‐mediated potentiation of cAMP responses is not secondary to activation of phosphoinositide hydrolysis and is likely mediated by a group II mGluR.