Premium
Developmental Changes in the Modulation of Cyclic AMP Formation by the Metabotropic Glutamate Receptor Agonist 1 S ,3 R ‐Aminocyclopentane‐1,3‐Dicarboxylic Acid in Brain Slices
Author(s) -
Casabona G.,
Genazzani A. A.,
Stefano M.,
Sortino M. A.,
Nicoletti F.
Publication year - 1992
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 - 10.1111/j.1471-4159.1992.tb08360.x
Subject(s) - metabotropic glutamate receptor , metabotropic receptor , metabotropic glutamate receptor 5 , neuroscience , agonist , metabotropic glutamate receptor 2 , glutamate receptor , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 6 , chemistry , metabotropic glutamate receptor 4 , metabotropic glutamate receptor 7 , receptor , psychology , biochemistry
Metabotropic glutamate receptors (mGluRs) have been recently described as a family of guanine nucleotide‐binding regulatory protein‐coupled receptors with multiple signal transduction pathways. At least one of these receptors appears to be negatively coupled to adenylyl cyclase when stably expressed in transfected cells. We have studied how activation of native mGluRs modulates cyclic AMP (cAMP) formation in brain slices prepared from rats at different ages. 1 S,3 R ‐1‐Aminocyclopentane‐1,3‐dicarboxylic acid (1 S , 1 R ‐ACPD), a selective agonist of mGluRs, slightly increased basal cAMP formation but reduced forskolin‐stimulated cAMP formation in adult hippocampal slices, in agreement with previous results. The action of 1 S ,3 R ‐ACPD on basal cAMP formation was not reproduced by the ionotropic receptor agonists N ‐methyl‐d‐aspartate, kainate, and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate and was antagonized by l‐2‐amino‐3‐phosphonopro‐pionate (l‐AP‐3). l‐AP‐3, however, did not prevent but rather mimicked the inhibitory action of 1 S ,3 R ‐ACPD on forskolin‐stimulated cAMP formation. In hippocampal slices from 1‐, 8‐, or 15‐day‐old rats, 1 S ,3 R ‐ACPD increased basal cAMP formation but failed to reduce the action of forskolin. A similar developmental pattern of modulation was observed in hypothalamic slices with the difference that 1 S ,3 R ‐ACPD did not stimulate basal cAMP formation in the hypothalamus of adult animals. These results suggest that inhibition of forskolin‐stimulated cAMP formation by 1 S ,3 R ‐ACPD is mediated by a specific mGluR subtype that is preferentially expressed in the adult.