title: Modulation of adenylyl cyclase activity in rat striatal homogenate by dopaminergic receptors.
abstract: 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.
authors.affiliation: Institute of Chemistry, University of Tartu, Jakobi 2, Tartu, Estonia.
authors.forename: Argo
authors.initials: A
authors.lastname: Vonk
authors.forename: Reet
authors.initials: R
authors.lastname: Reinart
authors.forename: Ago
authors.initials: A
authors.lastname: Rinken
mesh_terms: 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
chemical_list: 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