Brain calcium channel related dihydropyridine and phenylalkylamine binding sites in Alzheimer's, Parkinson's and Huntington's diseases.
Disruptions of normal calcium (Ca2+) homeostasis in human aging processes, are well documented. The existence of at least four distinct types of Ca2+ channels, L-, T-, P-, and N-, have been reported in the central nervous system. Binding sites for clinically useful dihydropyridines (DHP) and phenylalkylamines (PA) are located on the L-type Ca2+ channels. In the present study, DHP/[3H]PN200-110 and PA/[3H](-)-D-888 binding parameters were determined in various brain areas obtained at autopsy from Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) disease patients, and healthy age-matched controls as a means to assess the integrity of L-type channels in these neurological disorders often associated with the aging brain. DHP and PA receptor binding parameters (KD and Bmax) were not significantly altered in any of the brain regions studied in AD and PD. However, a significant decrease in the maximal binding capacity of [3H]PN200-110 was observed in the striatum of HD patients. Taken together, this suggests that DHP and PA binding sites associated to L-type Ca2+ channels are mostly preserved in AD and PD brains. Accordingly, the use of DHP- and/or PA-related drugs in these neurological disorders should not be hindered by deficits in their related Ca2+ channel binding proteins.
Sen
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AP
Douglas Hospital Research Centre, Verdun, Que., Canada.
Boksa
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P
Quirion
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R
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001344:Autopsy; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D004095:Dihydropyridines / Q000378:metabolism; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D017275:Isradipine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D010300:Parkinson Disease / Q000378:metabolism*; D012016:Reference Values; D014700:Verapamil / Q000031:analogs & derivatives* / Q000378:metabolism
D015220:Calcium Channels; D004095:Dihydropyridines; C043184:4-desmethoxyverapamil; D014700:Verapamil; D002118:Calcium; D017275:Isradipine