Phosphorylation of membrane proteins in response to persistent stimulation of adenylate cyclsae-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 suggestthat 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.