title: Defective protein phosphorylation associated with hypofunctions in stroke-prone spontaneously hypertensive rat platelets.
abstract: The mechanism of platelet dysfunctions in stroke-prone spontaneously hypertensive rats (SHRSP) was investigated. Platelet aggregation was inversely correlated with blood pressure or heart weight/body weight ratios in various strains of spontaneously hypertensive rats (SHR), indicating genetic defects. Thrombin-induced 47 kDa protein phosphorylation was markedly reduced in platelets of SHRSP compared with that in Wistar-Kyoto (WKY) rat platelets, accompanying reduced aggregation and secretion, but in 20 kDa protein phosphorylation was unchanged. Ca2+ ionophore A23187-induced responses were also significantly decreased in SHRSP, and the degrees of the changes were greater than those by thrombin. However, 12-O-tetradecanoylphorbol 13-acetate-induced responses in SHRSP were similar to those in WKY rats, suggesting that protein kinase C activity and its substrate were normally present in SHRSP platelets. Phosphatidylinositol content in platelets of SHRSP was 20% less than that in WKY rat platelets, but the contents of other phospholipids, including phosphatidylinositol-4-monophosphate and phosphatidylinositol-4,5-bisphosphates, were unaltered. Thrombin-induced formation of diacylglycerols and phosphatidic acid did not differ from each other at the low concentrations. In the absence of Ca2+, thrombin-induced responses occurred to a similar degree in both platelets, whereas the enhancements by Ca2+ were much greater in WKY rats than in SHRSP. These results suggested that defective Ca2+ functions in receptor-mediated activation of protein kinase C and postkinase-mediated events appear to be an underlying mechanism for the hypofunctions in SHRSP platelets.
authors.affiliation: University of Shizuoka School of Pharmaceutical Sciences, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Mitubori
authors.forename: K
authors.initials: K
authors.lastname: Umegaki
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D001794:Blood Pressure; D001798:Blood Proteins / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002561:Cerebrovascular Disorders / Q000209:etiology*; D004075:Diglycerides / Q000096:biosynthesis; D004198:Disease Susceptibility; D006973:Hypertension / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D004075:Diglycerides; D010712:Phosphatidic Acids; D010743:Phospholipids; D000001:Calcimycin; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium