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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zheng, J. Nicholson, R. A. Lees, G. Verdon, B. Ganelli, C. R. |
| Description | Author Affiliation: Verdon B ( Institute of Pharmacy and Chemistry, School of Sciences, University of Sunderland, Wharncliffe Street, Sunderland SR2 3SD, UK.) |
| 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 microM 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 (IC(50), 13. 9 microM). 4. The cis isomer stereoselectively blocked veratridine-induced (but not K(+)-induced) [(3)H]-GABA release from mouse synaptosomes (IC(50), 4.6 microM). 5. At 20 microM cis-oleamide, but not trans, produced a marked inhibition of Na(+) channel-dependent rises in intrasynaptosomal Ca(2+). 6. The physiological significance of these observations was examined by isolating Na(+) spikes in cultured pyramidal neurones. Sixty-four microM 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 EC(50) of 4.1 microM 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 an important regulator of arousal. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 129 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2000-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Central Nervous System Depressants Pharmacology GABA-A Receptor Antagonists Ion Channel Gating Drug Effects Oleic Acids Sodium Channels Animals Cells, Cultured Cerebral Cortex Cytology Metabolism Electrophysiology Fluorometry Ligands Membrane Potentials Mice Neurotransmitter Agents Patch-Clamp Techniques Receptors, Drug Receptors, Presynaptic Stereoisomerism Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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