Ca2+ transport by the synaptosomal plasma membrane Ca2+-ATPase and the effect of thioridazine.
Thioridazine inhibits the activity of the synaptic plasma membrane Ca(2+)-ATPase from pig brain and slightly decreases the rate of Ca(2+) accumulation by synaptic plasma membrane vesicles in the absence of phosphate. However, in the presence of phosphate, thioridazine increases the rate of Ca(2+) accumulation into synaptic plasma membrane vesicles. Phosphate anions diffuse through the membrane and form calcium phosphate crystals, reducing the free Ca(2+) concentration inside the vesicles and the rate of Ca(2+) leak. The higher levels of Ca(2+) accumulation obtained in the presence of thioridazine could be explained by a reduction of the rate of slippage on the plasma membrane ATPase.
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain.
Javier
J
Palacios
M Rosario
MR
Sepúlveda
Anthony G
AG
Lee
Ana M
AM
Mata
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology; D010539:Permeability / Q000187:drug effects; D013552:Swine; D013572:Synaptic Vesicles / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013881:Thioridazine / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology
D016227:Benzoquinones; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; C105931:tetrahydroxy-1,4-benzoquinone; D014638:Vanadates; D000252:Calcium-Transporting ATPases; D013881:Thioridazine; D002118:Calcium