Amyloid beta peptide 1-40 and the function of rat hippocampal hemicholinium-3 sensitive choline carriers: effects of a proteolytic degradation in vitro.
Effects of amyloid beta peptide 1-40 (Abeta) and of plant cysteine proteases bromelain and papain on the high-affinity uptake of choline (HACU) and the specific binding of [3H]hemicholinium-3 ([3H]HC-3) have been investigated on hippocampal synaptosomes from young adult male Wistar rats under basal and stimulated conditions (55 mM KCl). Depolarization increased significantly the HACU levels (the changes were predominantly in Vmax) and mildly the [3H]HC-3 binding (the changes especially in K(D)). Nonaggregated Abeta at low nM concentrations suppressed the depolarization effects but was ineffective under basal conditions during a short-term incubation. Higher microM concentrations decreased the HACU and binding under basal conditions in a time-dependent manner. The binding changes were firstly associated with alterations in K(D) and secondarily were accompanied also by a drop in Bmax. The results suggest that Abeta directly influences high-affinity carriers, inhibits their transport activity and enhances their sensitivity to proteoLytic cleavage. Stimulation increases the sensitivity of carriers to the interaction with Abeta.
Kristofiková
Z
Z
Prague Psychiatric Centre, Czech Republic.
Tejkalová
H
H
Klaschka
J
J
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D006426:Hemicholinium 3 / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D006426:Hemicholinium 3; D002794:Choline