Possible involvement of G-proteins in the regulation of striatal dopamine D2 receptor affinity by cholecystokinin octapeptide.
A G(i)-protein antibody AS/7 at 1:10 dilution significantly increased the K(d) values of the D2 agonist [3H]N-propylnorapomorphine (NPA) binding sites in the rat striatal membranes, and coincubation with sulphated cholecystokinin octapeptide (CCK-8; 1 nM) did not further increase the K(d) values. A GTP analogue guanylyl-imidodiphosphate (GMP-PNP) at 100 microM markedly increased the K(d) values of the [3H]NPA binding sites 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 present results indicate that abnormal activity of G-proteins abolished the ability of CCK-8 to reduce the D2 receptor affinity in the brain.
Li
X M
XM
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Jansson
A
A
Finnman
U B
UB
Agnati
L F
LF
Fuxe
K
K
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism / Q000502:physiology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology*
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D006165:Guanylyl Imidodiphosphate; C009074:N-n-propylnorapomorphine; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D012844:Sincalide; D001058:Apomorphine