Reduced functions of intracellular Ca2+ in aggregation, secretion and protein phosphorylation of permeabilized platelets from stroke-prone spontaneously hypertensive rats.
Aggregation, secretion and 47kDa protein (P47) phosphorylation by various agonists such as thrombin, ADP and ionophore A23187 were markedly reduced in platelets from stroke-prone spontaneously hypertensive rats (SHRSP) compared with those of age-matched Wistar Kyoto rat (WKY) platelets, suggesting defective functions of intracellular Ca2+ in SHRSP platelets (Tomita et al. Hypertension 1989; 14: 304-315). To clarify the mechanism of the platelet hypofunctions, saponin permeabilized platelets were prepared to compare the responses of platelets from both rats in varying concentrations of extracellular Ca2+. The leakage of lactate dehydrogenase from saponin (15 micrograms/ml)-treated platelets was approx. 5% of total activity; the degree of the leakage in both platelets did not differ. In saponin-treated platelets, extracellular Ca2+ alone did not induce either aggregation or secretion in both strains. However, in the presence of 1-oleoyl-2-acetylglycerol (10 micrograms/ml), Ca2+ dose dependently stimulated both aggregation and secretion. Under this condition, Ca2+ sensitivity of aggregation, secretion and P47 phosphorylation in SHRSP platelets were significantly reduced compared with those in WKY platelets. These results strongly suggest that intracellular Ca2+ functions are impaired in SHRSP platelets.
Ikeda
M
M
Graduate School of Health Sciences, University of Shizuoka, Japan.
Onda
T
T
Tomita
I
I
Tomita
T
T
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology; D006973:Hypertension / Q000097:blood*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012503:Saponins / Q000494:pharmacology
D001798:Blood Proteins; D004075:Diglycerides; D012503:Saponins; C038237:1-oleoyl-2-acetylglycerol; D007770:L-Lactate Dehydrogenase; D002118:Calcium