Reduced G(s) protein function and G alpha(s) levels in leukocytes of patients with Parkinson's disease

被引:6
作者
Avissar, S
BarkiHarrington, L
Herishanu, Y
Schreiber, G
机构
[1] BEN GURION UNIV NEGEV,FAC HLTH SCI,DEPT NEUROL,IL-84105 BEER SHEVA,ISRAEL
[2] BEN GURION UNIV NEGEV,FAC HLTH SCI,DEPT PSYCHIAT,IL-84105 BEER SHEVA,ISRAEL
关键词
G protein; Parkinson's disease; receptor;
D O I
10.1002/mds.870120206
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Early events in signal information transduction beyond dopamine, beta-adrenergic, and muscarinic receptors, involving receptor-coupled G-protein function and Get subunit immunoreactive levels were measured in mononuclear leukocytes (MNLs) of 12 never-treated patients with Parkinson's disease in comparison with 10 age- and sex-matched healthy control subjects. Both beta-adrenergic and dopamine receptor-coupled GS protein function as measured by cholera toxin-sensitive, isoproterenol- and dopamine-induced increases in Gpp(NH)p-binding capacity, in MNLs of patients with Parkinson's disease were found to be significantly reduced in comparison with those in the control group, Muscarinic receptor-coupled non-G(s) (G(i) or G(o)) protein function: pertussis toxin-sensitive, carbamylcholine-induced increase in Gpp(NH)p-binding capacity, was not found to be significantly different between patients with Parkinson's disease and control subjects. G protein a subunits were measured through immunobloting analyses with specific polyclonal antibodies against G alpha(s), G alpha(i), and G alpha(q) subunits, MNL levels of the 45-kDa species of G alpha(s) were found to be significantly reduced in patients with Parkinson's disease in comparison with control subjects. Other non-G(s) proteins (G(i), G(q)) did not show any significant quantitative differences between patients with Parkinson's disease and control subjects. The reductions in G alpha(s) levels in MNLs of patients with Parkinson's disease may explain the beta-adrenergic and dopamine receptor-coupled G(s) protein hypofunction detected in MNLs of these patients. As previous studies have failed to observe significant changes in receptor levels in MNLs of patients with Parkinson's disease, our findings of reduced dopaminergic and beta-adrenergic receptor-coupled G(s) function and of G alpha(s) immunoreactive levels in MNLs of Parkinson's patients point to alterations distal to these receptors at the level of the signal-transducing G(s) protein.
引用
收藏
页码:167 / 174
页数:8
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