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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shirasaki, T. Akaike, N. Munakata, M. Yakushiji, T. Hirata, A. |
| Description | Author Affiliation: Yakushiji T ( Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.) |
| Abstract | 1. The effects of benzodiazepine receptor (BZR) partial agonists, Y-23684 and CL218,872, were compared with its full agonist, diazepam, on gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) in acutely dissociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spinal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp technique. 2. The GABA-induced responses were essentially the same in both SVH and CPJ neurones, but the KD value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3. Enhancement of the GABA response by the two partial agonists was about one-third of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ2, is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ1, is predominant). In CTX neurones where both type I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4. In concentration-response relationships of BZR partial agonists, the threshold concentrations, KD values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and KD values of diazepam action were 10 fold less than those induced by partial agonists. 5. All BZR agonists shifted the concentration-response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ1 and BZ2 increase the affinity of the GABAA receptor for GABA. 6. The results are important in clarifying the mechanism of anxiety and might explain the anxioselectivity of BZR partial agonists. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 109 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1993-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Central Nervous System Cytology Neurons Drug Effects Receptors, GABA-A Aging Metabolism Animals Benzothiepins Pharmacology Cerebral Cortex Diazepam In Vitro Techniques Membrane Potentials Purkinje Cells Pyridazines Rats, Wistar Spinal Cord Tranquilizing Agents Gamma-Aminobutyric Acid Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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