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Titolo:
D-1 dopamine receptor activation reduces GABA(A) receptor currents in neostriatal neurons through a PKA/DARPP-32/PP1 signaling cascade
Autore:
Flores-Hernandez, J; Hernandez, S; Snyder, GL; Yan, Z; Fienberg, AA; Moss, SJ; Greengard, P; Surmeier, DJ;
Indirizzi:
Northwestern Univ, Sch Med, Dept Physiol, NUIN, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 ysiol, NUIN, Chicago, IL 60611 USA Northwestern Univ, Sch Med, Inst Neurosci, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 st Neurosci, Chicago, IL 60611 USA Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA Rockefeller Univ New York NY USA 10021 urosci Lab, New York, NY 10021 USA Univ Coll London, MRC, Mol Cell Biol Lab, London WC1E 6BT, England Univ Coll London London England WC1E 6BT l Lab, London WC1E 6BT, England Univ Coll London, Dept Pharmacol, London WC1E 6BT, England Univ Coll London London England WC1E 6BT macol, London WC1E 6BT, England
Titolo Testata:
JOURNAL OF NEUROPHYSIOLOGY
fascicolo: 5, volume: 83, anno: 2000,
pagine: 2996 - 3004
SICI:
0022-3077(200005)83:5<2996:DDRARG>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-AMINOBUTYRIC-ACID; PROTEIN-KINASE-A; RAT STRIATAL NEURONS; MEDIUM SPINY NEURONS; GATED CHLORIDE FLUX; CHOLINERGIC INTERNEURONS; BRAIN SYNAPTONEUROSOMES; CA2+ CONDUCTANCE; GLOBUS-PALLIDUS; BETA SUBUNITS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Flores-Hernandez, J Northwestern Univ, Sch Med, Dept Physiol, NUIN, 320 E Super St, Chicago, IL 60611 USA Northwestern Univ 320 E Super St Chicago ILUSA 60611
Citazione:
J. Flores-Hernandez et al., "D-1 dopamine receptor activation reduces GABA(A) receptor currents in neostriatal neurons through a PKA/DARPP-32/PP1 signaling cascade", J NEUROPHYS, 83(5), 2000, pp. 2996-3004

Abstract

Dopamine is a critical determinant of neostriatal function, but its impacton intrastriatal GABAergic signaling is poorly understood The role of D-1 dopamine receptors in the regulation of postsynaptic GABA(A) receptors was characterized using whole cell voltage-clamp recordings in acutely isolated, rat neostriatal medium spiny neurons. Exogenous application of GABA evoked a rapidly desensitizing current that was blocked by bicuculline. Application of the D-1 dopamine receptor agonist SKF 81297 reduced GABA-evoked currents in most medium spiny neurons. The D-1 dopamine receptor antagonist SCH23390 blocked the effect of SKF 81297. Membrane-permeant cAMP analogues mimicked the effect of D-1 dopamine receptor stimulation, whereas an inhibitor of protein kinase A (PKA; Rp-8-chloroadenosine 3',5' cyclic monophosphothioate) attenuated the response to D-1 dopamine receptor stimulation or cAMPanalogues. Inhibitors of protein phosphatase 1/2A potentiated the modulation by cAMP analogues. Single-cell RT-PCR profiling revealed consistent expression of mRNA for the beta 1 subunit of the GABA(A) receptor-a known substrate of PKA-in medium spiny neurons. Immunoprecipitation assays of radiolabeled proteins revealed that D-1 dopamine receptor stimulation increased phosphorylation of GABA(A) receptor beta 1/beta 3 subunits. The D-1 dopamine receptor-induced phosphorylation of beta 1/beta 3 subunits was attenuated significantly in neostriata from DARPP-32 mutants. Voltage-clamp recordings corroborated these results, revealing that the efficacy of the D-1 dopamine receptor modulation of GABA(A) currents was reduced in DARPP-32-deficient medium spiny neurons. These results argue that D-1 dopamine receptor stimulation in neostriatal medium spiny neurons reduces postsynaptic GABA(A) receptor currents by activating a PKA/DARPP-32/protein phosphatase 1 signaling cascade targeting GABA(A) receptor beta 1 subunits.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 13:35:55