Chronic desipramine treatment influences D1 stimulation and D2 inhibition (dual control) of adenylate cyclase by dopamine in rat striatum.
The response of adenylate cyclase to GTP and to dopamine (DA) was investigated in striatal membranes from desipramine (DMI)- or saline-treated rats. DMI (15 mg/kg) or saline was injected i.p. once a day for 3 weeks. In saline-treated control membranes, GTP exerted a biphasic effect on basal and DA-stimulated enzyme activity; peak levels of stimulation by DA plus GTP were observed at 1 microM GTP. On the other hand, peak levels moved to the right in the GTP dose response curve in DMI-treated membranes. Therefore, D2 inhibition might be attenuated, while the D2 specific agonist, PPHT, was not observed to cause inhibition of adenylate cyclase. Furthermore, D1 stimulation of adenylate cyclase via D1 specific agonist SKF was attenuated in DMI-treated membranes. It seems, therefore, that chronic treatment of rat striatum with DMI exerts a dual influence, that is, a lessening of both D1 stimulation and D2 inhibition of adenylate cyclase, and alters specifically the overall process of the adenylate cyclase system.
Okada
F
F
Health Administration Center, Hokkaido University, Sapporo, Japan.
Horikawa
T
T
Tokumitsu
Y
Y
Nomura
Y
Y
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D003891:Desipramine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D006160:Guanosine Triphosphate; D002217:Carbachol; D000262:Adenylyl Cyclases; D003891:Desipramine; D004298:Dopamine