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Molecular link between membrane cholesterol and Na + /H + exchange within human platelets
Author(s) -
Kochhar N.,
Kaul D.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80090-4
Subject(s) - platelet , cholesterol , chemistry , phospholipase c , phospholipid , liposome , membrane , biochemistry , phospholipase , phospholipase a2 , cytoplasm , enzyme , medicine
Incubation of human platelets with cholesterol‐poor, cholesterol‐normal and cholesterol‐rich liposomes revealed that: (i) acquisition or depletion of platelet membrane cholesterol was highly selective; (ii) variation in membrane cholesterol was highly selective. Variation in membrane cholesterol content (cholesterol‐to‐phospholipid molar ratio from 0.15–1.2) with respect to values found in unmodified normal platelets, was paralleled by the observed changes in amiloride‐sensitive cytoplasmic pH, as well as phospholipase A 2 activity. However, a decrease in cytoplasmic pH was accompanied by an increase in phospholipase A 2 activity; (iii) membrane cholesterol‐modulated changes in intra‐platelet pH, as well as phospholipase A 2 activity, was completely inhibited when platelets were pretreated with quinacrine (a specific phospholipase A 2 inhibitor) before exposure to various types of liposomes. Although exposure of platelets (pretreated with amiloride) with various types of liposomes resulted in the inhibition of Na + /H + exchange it had no noticeable effect upon the observed phospholipase A 2 activity. Based upon these results we suggest that membrane cholesterol‐modulated phospholipase A 2 activity may be the basic mechanism responsible for the nature of Na + /H + exchanger activity observed in cholesterol‐enriched platelets, leading these platelets to a hypersensitized state.