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Titolo:
(S)-4-CARBOXY-3-HYDROXYPHENYLGLYCINE ACTIVATES PHOSPHATIDYL-INOSITOL LINKED METABOTROPIC GLUTAMATE-RECEPTOR IN DIFFERENT BRAIN-REGIONS OF THE NEONATAL RAT
Autore:
SACAAN AI; SANTORI EM; RAO TS;
Indirizzi:
SIBIA NEUROSCI INC,NEUROPHARMACOL LAB,505 COAST BLVD S LA JOLLA CA 92037
Titolo Testata:
Neurochemistry international
fascicolo: 1, volume: 32, anno: 1998,
pagine: 77 - 85
SICI:
0197-0186(1998)32:1<77:(APL>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; CYCLIC-AMP FORMATION; MGLUR1 MUTANT MICE; PHENYLGLYCINE DERIVATIVES; MESSENGER-RNA; SUBTYPES; ANTAGONIST; AGONIST; ACID; TRANSPORTERS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
A.I. Sacaan et al., "(S)-4-CARBOXY-3-HYDROXYPHENYLGLYCINE ACTIVATES PHOSPHATIDYL-INOSITOL LINKED METABOTROPIC GLUTAMATE-RECEPTOR IN DIFFERENT BRAIN-REGIONS OF THE NEONATAL RAT", Neurochemistry international, 32(1), 1998, pp. 77-85

Abstract

In the present investigation, effects of several agonists and antagonists of metabotropic glutamate receptors (mGluRs) which are coupled tophosphatidyl inositol (PI) hydrolysis were evaluated in slices of neonatal rat hippocampus, striatum, cortex and cerebellum. The rank orderof potency of agonists in the PI hydrolysis assay was identical in all brain regions: quisqualic acid (Quis)>(RS)-3,5-dihydroxyphenylglycine (3,5-DHPG)>1S,3R-aminocyclopentane dicarboxylic acid (1S,3R-ACPD)>>L-glutamate (Glu). All agonists were equiefficacious in the four brain regions tested. The responses to 3,5-DHPG, a highly selective Class I mGluR agonist, were attenuated by (S)-4-carboxyphenylglycine ((S)-4CPG), (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG) and 1-aminoindan-1,5-dicarboxylic acid (UPF-523) with a rank order of potency of (+)-MCPG greater than or equal to(S)-4CPG greater than or equal to UPF-523 in the different brain regions. These results suggest little selectivity among these putative mGluR antagonists in the different brain regions studied. Interestingly, (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG), a compound reported to act as an antagonist at Class I mGluRs,produced concentration-dependent increases in PI hydrolysis in all four brain regions suggesting that (S)-4C3HPG acts as an agonist. In striatum, hippocampus and cortex, (S)-4C3HPG was equiefficacious to Quis,3,5-DHPG, 1S,3R-ACPD and Glu. However, in the cerebellum, (S)-4C3HPG displayed weak agonist activity (37% of that of a maximally effective concentration of Quis). The effects of(S)-4C3HPG in the PI hydrolysis assay appeared to be mediated by the activation of an mGluR subtype since it was significantly blocked by (S)-4CPG, an mGluR antagonist. In addition, the agonistic effects of (S)-4C3HPG appear to be unrelated to inhibition of [H-3]-Glu uptake into rat hippocampal or cerebellar synaptosomes. These results demonstrate a unique pharmacological profileof (S)-4C3HPG which can be interpreted as (S)-4C3HPG being a highly selective mGluR5 agonist or alternatively, that the effects of (S)-4C3HPG may be mediated through a novel Class I mGluR subtype(s), yet to beidentified. (C) 1998 Elsevier Science Ltd. All rights reserved.

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Documento generato il 28/11/20 alle ore 18:11:56