Striatal muscarinic receptors: Regulation by dopaminergic agonists |
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Authors: | Frederick J Ehlert William R Roeske Henry I Yamamura |
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Institution: | Departments of Pharmacology, Psychiatry and Internal Medicine University of Arizona Health Sciences Center Tucson, Arizona 85724, USA |
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Abstract: | The effects of apomorphine on the binding properties of striatal muscarinic receptors were investigated using the specific muscarinic antagonist, 3H](?)3-quinuclidinyl benzilate (3H](?)QNB). When binding measurements were made in 50 mM sodium/HEPES buffer, pH 7.4, containing Mg+2, the binding of 3H](?)QNB was consistent with the presence of two binding sites; 57% of the sites had a high affinity dissociation constant of 0.030 nM whereas the remaining sites had a low affinity dissociation constant of 0.64 nM. Apomorphine (1.0 μM) enhanced the binding of 3H](?)QNB by an apparent conversion of low to high affinity sites. A variety of other agents were screened for their ability to enhance 3H](?)QNB binding, and a pattern generally consistent with a dopaminergic effect was observed although some evidence for a β-adrenergic effect was demonstrable. The potent neuroleptics haloperidol, spiperone and sulpiride failed to antagonize the apomorphine enhancement of 3H](?)QNB binding as well as some adrenergic antagonists. However, the potent inhibitors of the dopamine-sensitive adenylate cyclase, α-flupenthixol and fluphenazine, specifically blocked the apomorphine enhancement of 3H](?)QNB binding with Ki values of approximately 0.1 μM. |
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