Inhibition of the human erythrocyte calcium pump by dimethyl sulfoxide.
The action of dimethyl sulfoxide on the human red cell Ca2+ pump was studied in inside-out vesicles. In a high-K+ medium at pH 7.6, the organic solvent inhibited both Ca2+ transport and ATP hydrolysis. Half-maximal effect was obtained with about 2% (v/v). At or below 10% dimethyl sulfoxide, the inhibition was overcome by adding inorganic phosphate or oxalate. In the absence of organic solvent, Ca2+ efflux from Ca(2+)-loaded vesicles consisted of a slow and a fast component whilst in its presence, there appears additionally a leakage component. The size of the latter depended markedly on dimethyl sulfoxide concentration, being about 3% at that level where Ca2+ uptake was half-maximally inhibited. ATP hydrolysis was more sensitive to dimethyl sulfoxide (10%) when free Ca2+ was increased within the millimolar level than when it was raised within the micromolar range. On the other hand, raising Ca2+ with organic solvent greatly stimulated ATP synthesis through ATP-Pi exchange, without reaching saturation. The results suggest that dimethyl sulfoxide blocks the red cell Ca2+ pump by increasing the affinity of the Ca2+ translocating site at the releasing step. They also show that at high concentrations, this solvent increases Ca2+ permeability.
Romero
P J
PJ
Instituto de Biología Experimental, Fac. Ciencias, Universidad Central de Venezuela, Caracas.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000838:Anions / Q000032:analysis; D001693:Biological Transport, Active / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D000254:Sodium-Potassium-Exchanging ATPase
D000838:Anions; D000001:Calcimycin; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D004121:Dimethyl Sulfoxide