REDUCED G(S) PROTEIN FUNCTION AND G-ALPHA(S) LEVELS IN LEUKOCYTES OF PATIENTS WITH PARKINSONS-DISEASE

Early events in signal information transduction beyond dopamine, beta- adrenergic, and muscarinic receptors, involving receptor-coupled G-pro tein function and Get subunit immunoreactive levels were measured in m ononuclear leukocytes (MNLs) of 12 never-treated patients with Parkins on's disease in comparison with 10 age- and sex-matched healthy contro l subjects. Both beta-adrenergic and dopamine receptor-coupled GS prot ein function as measured by cholera toxin-sensitive, isoproterenol- an d dopamine-induced increases in Gpp(NH)p-binding capacity, in MNLs of patients with Parkinson's disease were found to be significantly reduc ed in comparison with those in the control group, Muscarinic receptor- coupled non-G(s) (G(i) or G(o)) protein function: pertussis toxin-sens itive, carbamylcholine-induced increase in Gpp(NH)p-binding capacity, was not found to be significantly different between patients with Park inson's disease and control subjects. G protein a subunits were measur ed 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 reduc ed in patients with Parkinson's disease in comparison with control sub jects. Other non-G(s) proteins (G(i), G(q)) did not show any significa nt quantitative differences between patients with Parkinson's disease and control subjects. The reductions in G alpha(s) levels in MNLs of p atients with Parkinson's disease may explain the beta-adrenergic and d opamine receptor-coupled G(s) protein hypofunction detected in MNLs of these patients. As previous studies have failed to observe significan t changes in receptor levels in MNLs of patients with Parkinson's dise ase, 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 receptor s at the level of the signal-transducing G(s) protein.