Altered dopamine receptor mediated signal transmission in the striatum of aged rats.
Striatal membranes of very old (40 months) as against young (3 months) female Wistar rats were used. Binding saturation experiments with [3H]SCH 23390 at the dopamine (DA) D1 receptor (D1) and [3H]spiperone at the DA D2 receptor (D2) revealed no change in the affinity (Kd) but a significant decrease in the density (Bmax) of D1 (-31%, P < 0.005) and of D2 (-22%, P < 0.05), respectively, in the aged vs. young striata. Displacement of either [3H]SCH 23390 or [3H]spiperone binding by DA displayed biphasic curves. The Hill coefficient (nH) was significantly increased in the senescent compared with the young of D1 (0.72 +/- 0.04 vs. 0.61 +/- 0.03, P < 0.025) but unchanged of D2 (0.49 +/- 0.04 vs. 0.51 +/- 0.02). The proportion of the high-affinity agonist binding state (Rhigh) was significantly decreased (P < 0.025) in the older (20.9 +/- 3.2%) in comparison with the young (30.6 +/- 2.0%) in D1 but increased non-significantly in D2 (47.9 +/- 2.6 vs. 40.5 +/- 5.1%). Calculating the resulting Bmax from Scatchard and displacement analyses of each single aged and young animal revealed a highly significant reduction (P < 0.001) of the high-affinity agonist binding state of D1 (-53%) as well as a non-significant reduction of D2 (-8%) in the older. Simultaneously, a significant 57% decrease (P < 0.01) in the adenylate cyclase (AC) activity stimulated by 10 microM DA in the senescent compared with the young animals was monitored. The DA stimulation of AC was reversed in both cases by the addition of 200 nM of the D1 antagonist SCH 23390.
May
T
T
Department of Neuropsychopharmacology, Free University, Berlin, FRG.
Sugawa
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000254:growth & development / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D000262:Adenylyl Cyclases; D004298:Dopamine