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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wu, Y. N. Johnson, S. W. Shen, K. Z. |
| Description | Author Affiliation: Wu YN ( Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201, USA.) |
| Abstract | We used patch pipettes to record whole-cell currents from single dopamine neurons in slices of rat midbrain. Pharmacological methods were used to isolate EPSCs evoked by focal electrical stimulation. Baclofen was significantly more potent for inhibiting NMDA receptor-mediated EPSCs (IC50=0.24 microM) compared with inhibition of EPSCs mediated by AMPA receptors (IC50=1.72 microM). The increased potency of baclofen for inhibiting the NMDA component persisted in superfusate that contained zero Mg2+ and when postsynaptic K+ conductances were reduced by Cs+ and QX-314. Effects of baclofen on EPSCs were blocked by the GABA(B) receptor antagonist CGP-35348. Adenosine was 20 fold more potent for reducing the NMDA component of transmission (IC50=31 microM) compared with inhibition of AMPA receptor-mediated EPSCs (IC50=654 microM). Effects of adenosine on EPSCs were blocked by the A1 receptor antagonist DPCPX. Both baclofen and adenosine significantly increased the ratio of EPSCs in paired-pulse studies, suggesting presynaptic sites of action. Although adenosine (1 mM) did not reduce currents evoked by exogenous NMDA (10 microM), baclofen (1 microM) reduced NMDA currents by 29%. Neither baclofen nor adenosine altered currents evoked by exogenous AMPA (1 microM). We conclude that adenosine acts at presynaptic A1 receptors to cause a preferential reduction in the NMDA component of synaptic transmission. In contrast, baclofen preferentially reduces NMDA EPSCs by acting at both pre- and postsynaptic GABA(B) receptors. By regulating NMDA receptor function, A1 and GABA(B) receptors may play important roles in regulating the excitability of dopamine neurons. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Mesencephalon Physiology Neurons Receptors, N-Methyl-D-Aspartate Synaptic Transmission Adenosine Pharmacology Animals Baclofen Cesium Dopamine Metabolism Dose-Response Relationship, Drug Electrophysiology Excitatory Amino Acid Agonists Excitatory Postsynaptic Potentials Drug Effects GABA Agonists In Vitro Techniques Lidocaine Analogs & Derivatives Membrane Potentials N-Methylaspartate Cytology Presynaptic Terminals Rats, Sprague-Dawley Receptors, GABA-B Alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Research Support, U.S. Gov't, P.H.S. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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