POSSIBLE INVOLVEMENT OF G-PROTEINS IN THE REGULATION OF STRIATAL DOPAMINE D-2 RECEPTOR AFFINITY BY CHOLECYSTOKININ-OCTAPEPTIDE

A G(i)-protein antibody AS/7 at 1:10 dilution significantly increased the K-d values of the D-2 agonist [H-3]N-propylnorapomorphine (NPA) bi nding sites in the rat striatal membranes, and coincubation with sulph ated cholecystokinin octapeptide (CCK-8; 1 nM) did not further increas e the K-d values. A GTP analogue guanylyl-imidodiphosphate (GMP-PNP) a t 100 mu M markedly increased the K-d values of the [H-3]NPA binding s ites in the rat forebrain sections, and coincubation with CCK-8 (1 nM) again did not produce a further increase in the K-d values. The prese nt results indicate that abnormal activity of G-proteins abolished the ability of CCK-8 to reduce the D-2 receptor affinity in the brain. (C ) 1997 Elsevier Science Ireland Ltd.