Is dopamine-sensitive adenylate cyclase involved in regulating the activity of striatal cholinergic neurons?

Abstract

The dopamine (DA)-receptor mediated changes in striatal acetylcholine (ACh) levels have been studied to determine if this effect involves a D1-(adenylate cyclase dependent) or D2-(not linked to an adenylate cyclase) type of DA-receptor, Various DA-agonists (apomorphine, N-diphenethylamine derivatives) increased striatal ACh levels in both intact and 6-OHDA lesioned rats whereas only apomorphine stimulated the adenylate cyclase activity of striatal homogenates. The N-diphenethylamine compounds (RU 24213, RU 24926 and RU 26933) were without effect either on basal or DA-stimulated activities of this enzyme. In contrast, D-LSD (which acts as a partial agonist of the striatal DA-sensitive adenylate cyclase) did not modify the striatal ACh content. More interestingly, an intrastriatal injection of cholera toxin greatly stimulated striatal adenylate cyclase without altering ACh concentrations. Both haloperidol and methergoline antagonized the DA stimulation of adenylate cyclase, but only haloperidol decreased striatal ACh levels. These results indicate that the DA receptor involved in regulating the activity of striatal cholinergic neurons is of the D2-type.