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

Early events in signal information transduction beyond dopamine, β-adrenergic, and muscarinic receptors, involving receptor-coupled G-protein function and Gα 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 β-adrenergic and dopamine receptor-coupled G(s) 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 com parison 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 or subunits were measured through immunobloting analyses with specific polyclonal antibodies against Gα(s), Gα(i), and Gα(q) subunits. MNL levels of the 45-kDa species of Gα(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 Gα(s) levels in MNLs of patients with Parkinson's disease may explain the β-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 β-adrenergic receptor-coupled G(s) function and of Gα(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.