Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
MODULATION OF GABA(A) RECEPTORS AND INHIBITORY SYNAPTIC CURRENTS BY THE ENDOGENOUS CNS SLEEP REGULATOR CIS-9,10-OCTADECENOAMIDE (COA)
Autore:
LEES G; EDWARDS MD; HASSONI AA; GANELLIN CR; GALANAKIS D;
Indirizzi:
UNIV SUNDERLAND,SCH HLTH SCI,WHARNCLIFFE ST SUNDERLAND SR2 3SD ENGLAND UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,ST MARYS HOSP,SCH MED,ACAD DEPT ANAESTHET LONDON W2 1NY ENGLAND UNIV LONDON UNIV COLL,CHRISTOPHER INGOLD LABS,DEPT CHEM LONDON WC1H 0AJ ENGLAND
Titolo Testata:
British Journal of Pharmacology
fascicolo: 5, volume: 124, anno: 1998,
pagine: 873 - 882
SICI:
0007-1188(1998)124:5<873:MOGRAI>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT HIPPOCAMPAL-NEURONS; SINGLE AMINO-ACID; A RECEPTOR; BRAIN; SUBUNIT; CHANNEL; BENZODIAZEPINES; ANESTHETICS; CORTEX;
Keywords:
CIS-9,10-OCTADECENOAMIDE(OLEAMIDE) OLEIC ACID; GABA(A) RECEPTOR; FLUMAZENIL/BENZODIAZEPINE; RAT CULTURED CORTICAL NEURONS; HUMAN RECOMBINANT RECEPTORS; XENOPUS OOCYTES; ELECTROPHYSIOLOGY PATCH CLAMP; ENDOGENOUS SLEEP REGULATOR; INHIBITORY POSTSYNAPTIC POTENTIALS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
G. Lees et al., "MODULATION OF GABA(A) RECEPTORS AND INHIBITORY SYNAPTIC CURRENTS BY THE ENDOGENOUS CNS SLEEP REGULATOR CIS-9,10-OCTADECENOAMIDE (COA)", British Journal of Pharmacology, 124(5), 1998, pp. 873-882

Abstract

1 Cis-9,10-octadecenoamide (cOA) accumulates in the CSF of sleep-deprived cats and may represent a novel signalling molecule. Synthetic cOAhas been shown to induce physiological sleep when injected into laboratory rats. Here we assess the cellular mode of action of cOA in vitro. 2 In all rat cultured cortical neurones (pyramidal cells) examined, the synthetic brain lipid (3.2-64 mu M) enhanced the responses to subsaturating GABA concentrations (up to circa 2x) in a concentration-dependent manner (EC50, circa 15 mu M). 3 (20 mu M) cOA significantly enhanced the affinity of exogenous GABA for its receptor without changing the Hill slope or the maximal response. These effects were not voltage-dependent or secondary to shifts in E-Cl. 4 In the absence of GABA, cOA directly evoked small inhibitory currents in a subpopulation (<7%) of sensitive cells. 5 20 mu M cOA reversibly enhanced the duration of spontaneous inhibitory post synaptic currents (cii.ca 2 fold) without significantly altering their amplitude. 6 At 32-64 mu M, cOA reversibly reduced the incidence and amplitude of both inhibitory post synapticcurrents (i.p.s.cs) and excitatory post synaptic currents (e.p.s.cs) in the cultured neuronal circuits in common with other depressant drugs acting at the GABAA receptor. 7 32 mu M Oleic acid did not modulate exogenous GABA currents or synaptic activity suggesting that cOAs actions are mediated through a specific receptor. 8 A specific, protein-dependent interaction with GABA(A) receptors was confirmed in Xenopus oocytes. Recombinant human receptors were modulated by 10 mu M cOA (and diazepam) only when a gamma(2) subunit was co-expressed with alpha(1)beta(2): the cOA response was not sensitive to the specific benzodiazepine antagonist flumazenil(1 mu M). 8 cOA may represent an endogenous ligand for allosteric modulatory sites on isoforms of GABA(A) receptorswhich are crucial for the regulation of arousal and have recently been implicated in the circadian control of physiological sleep.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 16:52:43