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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Neu, J. M. Tenn, C. C. Niles, L. P. |
| Description | Author Affiliation: Tenn CC ( Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.) |
| Abstract | 1. The effects of benzodiazepine receptor antagonists on the inhibition of forskolin-stimulated adenylate cyclase (AC) activity by various benzodiazepine (BZ) and indoleamine agonists in the rat striatum were investigated. 2. A biphasic inhibition of forskolin-stimulated AC activity by the peripheral-type agonist, Ro5-4864, and a multiphasic inhibition by the non-selective BZ, diazepam, was observed. One phase of AC inhibition is consistent with a Gi-coupled receptor-mediated action, whereas the other phases appear to involve a direct effect on the enzyme itself. 3. While the central-type antagonist, flumazenil, had no effect on the ability of Ro5-4864 to inhibit AC activity, the peripheral-type receptor ligand, PK 11195, abolished the first phase of inhibition. 4. PK 11195 and pertussis toxin were found to block the inhibitory effect of various BZs and the indoleamines, melatonin and 2-iodomelatonin, on induced AC activity. 5. Saturation binding studies, conducted at 30 degrees C with [3H]-diazepam revealed a single binding site in the rat striatum (KD = 19.3 +/- 0.80 nM) which significantly decreased in affinity in the presence of GTP (KD = 30.5 +/- 2.6 nM; P < 0.05). No significant change in Bmax was observed. 6. These findings indicate the presence of Gi-coupled BZ receptors in the rat striatum. Thus, suppression of cyclic AMP production may contribute to the diverse neuropharmacological effects of BZs, melatonin and related drugs. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 119 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1996-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adenylate Cyclase Drug Effects Metabolism Benzodiazepines Antagonists & Inhibitors Pharmacology Colforsin Corpus Striatum Enzymology Isoquinolines Adenylate Cyclase Toxin Animals Benzodiazepinones Diazepam Drug Interactions Flumazenil GABA-A Receptor Antagonists Guanosine Triphosphate Indoles Agonists Kinetics Pertussis Toxin Rats, Sprague-Dawley Stimulation, Chemical Virulence Factors, Bordetella Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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