Increased platelet reactivity to prostaglandin E1 in hypertension is linked with altered signal transduction.
Prostaglandin E1 has been shown to induce a greater accumulation of cAMP in platelets from spontaneously hypertensive (SHR) than in platelets from normotensive (Wistar-Kyoto, WKY) rats (Circ. Res. 1978;43:583-591. Thromb. Res. 1988;49:5-21). This study was conducted to determine the mechanisms of increased platelet reactivity to PGE1 in hypertension. The number of PGE1 binding sites/platelet (WKY 280 +/- 8, SHR 287 +/- 5) as well as the Kd for WKY (105 +/- 11 nmol/L) and SHR (120 +/- 14 nmol/L) were found to be similar in WKY and SHR rats. PGE1-induced GTPase activity was determined using WKY and SHR platelet membranes. The basal GTPase activity was similar in WKY and SHR platelets. Incubation of membranes with PGE1 (3 mumol/L) for 1 min increased GTPase activity by 46% in WKY and by 806% in SHR. Incubation of platelets with 1.0 mmol/L IBMX (3-isobutyl-1-methyl-xanthine) for 4 min resulted in a 327 +/- 57% and 320 +/- 11% increase in cAMP in WKY and SHR platelets, respectively. In other experiments, incubation of platelets with 3, 10 and 100 mumol/L forskolin, induced similar increases in cAMP levels in WKY (103 +/- 12%, 530 +/- 42%, 784 +/- 41%) and SHR (111 +/- 13%, 461 +/- 18%, 756 +/- 28%) platelets. These data lead us to suggest that the greater accumulation of cAMP induced by PGE1 in SHR than in WKY platelets is linked with altered PGE1-receptor mediated signal transduction at the G-protein level.
Huzoor-Akbar
Department of Biological Sciences, Ohio University, Athens 45701.
Dean
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Kornhauser
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000527:Alprostadil / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006973:Hypertension / Q000097:blood*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction
D005576:Colforsin; D000242:Cyclic AMP; D020558:GTP Phosphohydrolases; D000527:Alprostadil; D015056:1-Methyl-3-isobutylxanthine