Phosphorylation of membrane proteins in response to persistent stimulation of adenylate cyclase-linked dopamine receptors in slices of striatum.

Prolonged incubation of slices of striatum with agonists of D-1 dopamine receptors increased phosphorylation of at least 5 membrane protein bands. The extent of the increase in phosphate-incorporation depended on the concentration (10(-5) M-10(-4) M) of the agonist in the incubation medium and the duration of incubation (20 min or longer). Preincubation of slices with haloperidol (10(-6) M) greatly reduced, while (-)sulpiride (10(-6) M) failed to alter the increase of phosphorylation elicited by dopamine. Prolonged incubation of striatal slices with LY 141865 (10(-5) M) or isoproterenol (10(-5) M) increased the phosphate-incorporation only in one of the protein bands with an apparent molecular weight of 42,000. Incubation of striatal slices with cholera toxin increased the phosphorylation of protein bands in a similar way to those elicited by dopamine. The present results suggest that the increased phosphorylation of certain protein bands elicited by prolonged exposure of striatal slices to D-1 dopamine receptor agonists may be associated with the desensitization of dopamine-sensitive adenylate cyclase.