A circulating inhibitor of the platelet Na+,K+ adenosine triphosphatase (ATPase) enzyme in allergy.
Previous investigations have documented a reduced activity of the sodium-potassium-stimulated adenosine triphosphatase enzyme (Na+,K+ ATPase) in platelet membranes of allergic subjects. The purpose of this study was to determine if the reduced Na+,K+ ATPase activity was due to an enzyme inhibitor. Na+,K+ ATPase activity of a particulate fraction of sonicated platelets was determined by spectrophotometry in asymptomatic adults with and without allergy. The Na+,K+ ATPase level (mean, nanomoles per microgram of protein per minute; +/- STD) of allergic subjects (0.9 +/- 1.3) was lower (p less than 0.001) than that of nonallergic subjects (3.9 +/- 1.6). In contrast, when the same platelet fractions were frozen before assay, Na+,K+ ATPase was higher (p less than 0.005) in allergic subjects (6.0 +/- 1.4) than in nonallergic subjects (3.6 +/- 2.0). An inhibitor of canine kidney Na+,K+ ATPase was detected in the buffer in which these platelet fractions were frozen, allergic subjects (0.5% +/- 0.4% inhibition per microgram of protein) compared to nonallergic subjects (0.04% +/- 0.08%; p less than 0.005). The level of inhibition correlated positively with the postfreezing increase in platelet membrane Na+,K+ ATPase, suggesting a freezing-induced displacement of an inhibitor from the membrane. Plasma from these same subjects inhibited Na+,K+ ATPase activity of normal platelets, allergic subjects (70% +/- 31% inhibition) compared to nonallergic subjects (13% +/- 16%; p less than 0.001). These data suggest that the transport-enzyme defect observed in platelets from allergic subjects was due to a circulating Na+,K+ ATPase inhibitor. In vivo Na+,K+ ATPase inhibition in allergy could have profound effects on intracellular cation concentrations and broad implications for pathogenesis.
Skoner
D P
DP
Department of Pediatrics, University of Pittsburgh School of Medicine, Pa.
Gentile
D
D
Evans
R W
RW
D000328:Adult; D001249:Asthma / Q000097:blood* / Q000209:etiology; D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D005615:Freezing; D006801:Humans; D012221:Rhinitis, Allergic, Perennial / Q000097:blood* / Q000209:etiology; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood* / Q000209:etiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000097:blood
D000254:Sodium-Potassium-Exchanging ATPase