Relationship between enhanced phosphoinositide turnover and cellular responses in platelets from spontaneously hypertensive rats.
Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared to normotensive Wistar-Kyoto (WKY) controls. Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY rats by using 32P-labeled quiescent platelets. In unstimulated cells, both the rate and extent of 32P incorporation into individual inositol-containing phospholipids and phosphatidic acid (PA) were identical in SHR and WKY rats. This suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced phosphoinositide metabolism, when monitored as changes in 32P-PA, was significantly higher in SHR than in WKY rats. Following thrombin stimulation, 32P-PA formation likely reflects the initial agonist-receptor interaction; therefore, our results suggest that phospholipase C activity is enhanced in SHR platelets. Thus, it can be postulated that the observed hypersensitivity of SHR phospholipase C may play a role in the overall alteration of cell calcium handling and hence in the SHR platelet response.
Koutouzov
S
S
INSERM U7, Department of Pharmacology, Hospital Necker, Paris, France.
Remmal
A
A
Meyer
P
P
Marche
P
P
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006973:Hypertension / Q000097:blood*; D008297:Male; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000097:blood*; D010974:Platelet Aggregation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D012701:Serotonin; D013917:Thrombin