title: Dopa resistance in multiple-system atrophy: loss of postsynaptic D2 receptors.
abstract: Postmortem autoradiography was used to explore the mechanisms underlying L-dopa resistance in 2 patients with multiple-system atrophy. Indices of striatal presynaptic dopamine terminal loss and dopamine (D1 and D2) receptors were provided by 3H-mazindol, 3H-SCH 23390, and 125I-sulpiride binding. Neuronal loss, gliosis, and loss of postsynaptic D2 receptors preferentially involved the middle and posterior of the putamen, that region of the striatum most intimately involved in motor function. Loss of D1 receptors in the same area occurred in only 1 patient. These findings suggest that in multiple-system atrophy, resistance to L-dopa is due to a loss of putamental D2 receptors. The differential effects on D1 and D2 receptors in 1 patient implies that different subpopulations of striatal neurons were selectively involved.
authors.affiliation: Department of Neurology, Austin Hospital, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Churchyard
authors.forename: G A
authors.initials: GA
authors.lastname: Donnan
authors.forename: A
authors.initials: A
authors.lastname: Hughes
authors.forename: D W
authors.initials: DW
authors.lastname: Howells
authors.forename: D
authors.initials: D
authors.lastname: Woodhouse
authors.forename: J Y
authors.initials: JY
authors.lastname: Wong
authors.forename: R M
authors.initials: RM
authors.lastname: Kalnins
authors.forename: F A
authors.initials: FA
authors.lastname: Mendelsohn
authors.forename: G
authors.initials: G
authors.lastname: Paxinos
mesh_terms: D000368:Aged; D001284:Atrophy; D001345:Autoradiography; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011699:Putamen / Q000378:metabolism / Q000473:pathology; D017447:Receptors, Dopamine D1 / Q000032:analysis*; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D013569:Synapses / Q000378:metabolism
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007980:Levodopa