Enhanced adenylate cyclase activity in neonatally dopamine lesioned rats is related to increased Gs-protein coupling.
It has previously been shown that neonatal selective lesions of the central dopamine system with 6-hydroxydopamine lead to increased basal and dopamine-stimulated adenylate cyclase activity in striatum without any alterations of dopamine receptor binding characteristics. In the present study, it was shown that adenylate cyclase activity following G-protein stimulation by the GTP analogue 5-guanylimidodiphosphate (Gpp(NH)p) was increased in striatal preparations from neonatally 6-hydroxy-dopamine-lesioned rats, compared with control animals. No difference was seen in forskolin-stimulated enzyme activity between the two groups. These results indicate that neonatal dopamine lesions induce a selective functional supersensitivity at the D1 receptor complex by enhancing the coupling efficiency of the Gs protein to adenylate cyclase, without alterating the catalytic activity of the enzyme.
Cowburn
R
R
Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Young
D
D
Luthman
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D016627:Oxidopamine; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D004298:Dopamine