Striatal muscarinic receptors: Regulation by dopaminergic agonists

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 K_i values of approximately 0.1 μM.