Anatomy and function of dopamine receptors: understanding the pathophysiology of fluctuations in Parkinson's disease.
The principal dopamine (DA) receptors mediating the antiparkinson effects of levodopa are D1 and D2, which are anatomically and functionally segregated. We hypothesize that DA receptor-mediated effects are critical for the development of treatment-related fluctuations in Parkinson's disease (PD). We suggest that two sequential processes occur to permit the emergence of the so-called short duration response and dyskinesias: (1) functional uncoupling of D1 and D2 receptor-mediated effects with shift to the left of the dose-response curve; and, (2) sensitization of the D1-mediated striatal output due to repetitive, primarily D1 receptor stimulation by DA. These mechanisms result in excessive, pathological inhibition of basal ganglia output neurons in the GPi producing dyskinesias and the short duration response.
Wooten
G F
GF
Department of Neurology, University of Virginia Health System, Box 800394, Charlottesville, VA 22908, USA. gfw4b@virginia.edu
D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D010300:Parkinson Disease / Q000503:physiopathology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D014018:Tissue Distribution
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2