Solubilization of striatal D-2 dopamine receptors: evidence that apparent loss during aging is not due to membrane sequestration.

D-2 dopamine receptors from mature (3 to 6 months) and senescent (24 to 25 months) rat striatal membranes were solubilized with the detergent 3-(3-cholamidopropyl) dimethylammonio-2-hydroxy-1-propanesulfonate (CHAPSO). Essentially all of the receptors were recovered following CHAPSO treatment. Approximately 80 to 90% of the receptors were detected in the supernatant fraction under these conditions, with a small percentage remaining membrane bound in both age groups. A 10-fold reduction in binding affinity for [3H]spiperone was observed for solubilized receptors of both age groups. Ultra high speed centrifugation of untreated preparations (200,000 X g) revealed essentially no hidden D-2 dopamine receptors in the light membrane fraction from either mature or senescent rats. These results suggest that a decreased biosynthetic rate (Henry & Roth, 1984; Leff et al., 1984) rather than membrane sequestration accounts for loss of D-2 dopamine receptors with age.