Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Stereoselective modulatory actions of oleamide on GABA(A) receptors and voltage-gated Na+ channels in vitro: a putative endogenous ligand for depressant drug sites in CNS
Autore:
Verdon, B; Zheng, J; Nicholson, RA; Ganellin, CR; Lees, G;
Indirizzi:
Univ Sunderland, Inst Pharm & Chem, Sch Sci, Sunderland SR2 3SD, Durham, England Univ Sunderland Sunderland Durham England SR2 3SD R2 3SD, Durham, England Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada Simon FraserUniv Burnaby BC Canada V5A 1S6 , Burnaby, BC V5A 1S6, Canada Univ Coll London, Dept Chem, Christopher Ingold Labs, London, England UnivColl London London England hristopher Ingold Labs, London, England
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 129, anno: 2000,
pagine: 283 - 290
SICI:
0007-1188(200001)129:2<283:SMAOOO>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; SODIUM-CHANNELS; BRAIN LIPIDS; INDUCE SLEEP; NEURONS; ANESTHETICS; LAMOTRIGINE; MECHANISMS; CURRENTS; CELLS;
Keywords:
cis-9,10-octadecenoamide (oleamide); GABA(A) receptor; voltage-gated Na+ channel, sustained repetitive firing; cultured rat cortical neurons; mouse synaptoneurosomes/synaptosomes; transmitter release; intracellular Ca2+; hypnotic/anaesthetic/anticonvulsant drugs; electrophysiology/patch clamp; endogenous sleep regulator;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Lees, G Univ Sunderland, Inst Pharm & Chem, Sch Sci, Wharncliffe St, Sunderland SR2 3SD, Durham, England Univ Sunderland Wharncliffe St Sunderland Durham England SR2 3SD d
Citazione:
B. Verdon et al., "Stereoselective modulatory actions of oleamide on GABA(A) receptors and voltage-gated Na+ channels in vitro: a putative endogenous ligand for depressant drug sites in CNS", BR J PHARM, 129(2), 2000, pp. 283-290

Abstract

1 cis-9,10-octadecenoamide ('oleamide') accumulates in CSF on sleep deprivation. It induces sleep in animals (the trans form is inactive) but its cellular actions are poorly characterized. We have used electrophysiology in cultures from embryonic rat cortex and biochemical studies in mouse nerve preparations to address these issues.2 Twenty mu M cis-oleamide (but not trans) reversibly enhanced GABA(A) currents and depressed the frequency of spontaneous excitatory and inhibitory synaptic activity in cultured networks.3 cis-oleamide stereoselectively blocked veratridine-induced (but not K+-induced) depolarisation of mouse synaptoneurosomes (IC50, 13.9 mu M).4 The cis isomer stereoselectively blocked veratridine-induced (but not K+-induced) [H-3]-GABA release from mouse synaptosomes (IC50, 4.6 mu M).5 At 20 mu M cis-oleamide, but not trans, produced a marked inhibition of Na+ channel-dependent rises in intrasynaptosomal Ca2+.6 The physiological significance of these observations was examined by isolating Na+ spikes in cultured pyramidal neurones. Sixty-four mu M cis-oleamide did not significantly alter the amplitude, rate of rise or duration of unitary action potentials (1 Hz).7 cis-Oleamide stereoselectively suppressed sustained repetitive firing (SRF) in these cells with an EC50 of 4.1 mu M suggesting a frequency- or state-dependent block of voltage-gated Na+ channels.8 Oleamide is a stereoselective modulator of both postsynaptic GABA(A) receptors and presynaptic or somatic voltage-gated Na+ channels which are crucial for synaptic inhibition and conduction. The modulatory actions are strikingly similar to those displayed by sedative or anticonvulsant barbiturates and a variety of general anaesthetics.9 Oleamide may represent an endogenous modulator for drug receptors and animportant regulator of arousal.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:48:18