Brain calcium channel related dihydropyridine and phenylalkylamine binding sites in Alzheimer's, Parkinson's and Huntington's diseases

Abstract

Disruptions of normal calcium (Ca 2+) homeostasis in human aging process, are well documented. The existence of at least four distinct types of Ca 2+ channels, L-, T-, P-, and N-, have been reported in the centra l nervous system. Binding sites for clinically useful dihydropyridines (DPH) and phenylalkylamines (PA) are located on the L-type Ca 2+ 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 ( K D and B max) 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 Ca 2+ 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 Ca 2+ channel binding proteins.