Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats.
Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY 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 were identical in SHR and WKY. This finding 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]phosphatidic acid, was significantly higher in SHR than in WKY. For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more [32P]phosphatidic acid in SHR than in WKY. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced [32P]phosphatidic acid formation in SHR. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. Following thrombin stimulation, [32P]phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR.
Koutouzov
S
S
Institut National de la Santé et de la Recherche Médicale (INSERM U7), Department of Pharmacology, Hôpital Necker, Paris, France.
Remmal
A
A
Marche
P
P
Meyer
P
P
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006973:Hypertension / Q000097:blood*; D008297:Male; D010716:Phosphatidylinositols / Q000097:blood*; D010761:Phosphorus Radioisotopes / Q000378:metabolism; D010974:Platelet Aggregation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism; D010738:Type C Phospholipases / Q000097:blood*
D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D012701:Serotonin; D010738:Type C Phospholipases; D002118:Calcium