Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain slices as revealed by a new positron-based imaging technique
Murata, T. ; Matsumura, K. ; Sihver, S. ; Onoe, H. ; Bergström, M. ; Sihver, W. ; Yonekura, Y. ; Långström, B. ; Watanabe, Y.
Springer
Published 1998
Springer
Published 1998
| ISSN: |
1435-1463
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| Keywords: |
Keywords: Brain slice ; positron emitting tracer ; triazolam ; muscarinic acetylcholine receptor ; amnesia.
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| Source: |
Springer Online Journal Archives 1860-2000
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| Topics: |
Medicine
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| Notes: |
Summary. The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic acetylcholinergic receptor (mAChR) binding was investigated in living brain slices by use of a novel positron-based imaging technique. Fresh rat brain slices were incubated with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a mAChR antagonist, in oxygenated Krebs-Ringer solution at 37°C. During incubation, time-resolved imaging of [11C]NMPB binding in the slices was constructed on the storage phosphor screens. Addition of triazolam (1 μM) plus muscimol (30 μM), a GABAA receptor agonist, to the incubation mixture decreased the specific binding of [11C]NMPB. Ro15-1788, a BZ receptor antagonist, prevented this effect, indicating that the effect was exerted through the GABAA/BZ receptor complex. These results demonstrated that stimulation of the GABAA/BZ receptor lowers the affinity of the mAChR for its ligand, which may underlie the BZ-induced amnesia, a serious clinical side effect of BZ. No such effect in the P2-fraction instead implies that the integrity of the neuronal cells and/or their environment is prerequisite for the modulation of mAChR by GABAA/BZ stimulation.
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| Type of Medium: |
Electronic Resource
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| URL: |