Modulation of adenylyl cyclase activity in rat striatal homogenate by dopaminergic receptors.
We have characterized the modulation of adenylyl cyclase (AC) activity by ligands of dopaminergic receptors in rat striatal homogenate and compared the results with receptor-ligand binding affinities. Despite the fact that rat striatum contains high level of both dopamine D(1) and D(2) receptors, only the D(1)-specific AC activation by agonists could be determined. All D(1)-receptor agonists (dopamine, dihydrexidine, and A 77636) used were able to increase cAMP accumulation in a concentration-dependent manner, while D(1)-receptor antagonists (SCH23390, SKF83566, and butaclamol) blocked the effects induced by the aforementioned agonists. At the same time, the D(2)-receptor agonist quinpirole and antagonist sulpiride had no effect on cAMP accumulation in striatal homogenate neither on the basal level nor on the activated level of AC, while inhibited [(3)H]raclopride binding to these membranes. Comparing the ligands of the D(1) receptor in modulating the activity of AC and displacing D(1)-receptor-specific radioligand [(3)H]SCH23390 binding revealed that the ligands modulate both of these processes with similar affinities. It indicates that under given experimental conditions, only dopamine D(1)-receptor-mediated stimulation of AC activity can be measured in membrane homogenate of rat striatum, while dopamine D(2)-receptor effects remain fully hidden.
Vonk
Argo
A
Institute of Chemistry, University of Tartu, Jakobi 2, Tartu, Estonia.
Reinart
Reet
R
Rinken
Ago
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003627:Data Interpretation, Statistical; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D017072:Neostriatum / Q000201:enzymology* / Q000502:physiology*; D011869:Radioligand Assay; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007202:Indicators and Reagents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008274:Magnesium