Loss of high-affinity prostacyclin receptors in platelets and the lack of prostaglandin-induced inhibition of platelet-stimulated thrombin generation in subjects with spinal cord injury

被引:20
作者
Kahn, NN
Bauman, WA
Sinha, AK
机构
[1] VET AFFAIRS MED CTR,SPINAL CORD DAMAGE RES CTR,SPINAL CORD INJURY & RES SERV,BRONX,NY 10468
[2] MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029
[3] MT SINAI SCH MED,SPINAL CORD DAMAGE RES CTR,NEW YORK,NY 10029
[4] JADAVPUR UNIV,DEPT BIOTECHNOL,CALCUTTA 700032,W BENGAL,INDIA
关键词
D O I
10.1073/pnas.93.1.245
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Coronary artery disease is a leading cause of death in individuals with chronic spinal cord injury (SCI), However, platelets of those with SCI (n = 30) showed neither increased aggregation nor resistance to the antiaggregatory effects of prostacyclin when compared with normal controls (n = 30), Prostanoid-induced cAMP synthesis was similar in both groups, In contrast, prostacyclin, which completely inhibited the platelet-stimulated thrombin generation in normal controls, failed to do so in those with SCI. Scatchard analysis of the binding of [H-3]prostaglandin E(1), used as a prostacyclin receptor probe, showed the presence of one high-affinity (K-d1 = 8.11 +/- 2.80 nM; n(1) = 172 +/- 32 sites per cell) and one low-affinity (K-d2 = 1.01 +/- 0.3 mu M; n(2) = 1772 +/- 226 sites per cell) prostacyclin receptor in normal platelets. In contrast, the same analysis in subjects with SCI showed significant loss (P < 0.001) of high-affinity receptor sites (K-d1 = 6.34 +/- 1.91 nM; n(1) = 43 +/- 10 sites per cell) with no significant change in the low affinity-receptors (K-d2 = 1.22 +/- 0.23; n(2) = 1820 +/- 421). Treatment of these platelets with insulin, which has been demonstrated to restore both of the high- and low-affinity prostaglandin receptor numbers to within normal ranges in coronary artery disease, increased high-affinity receptor numbers and restored the prostacyclin effect on thrombin generation. These results demonstrate that the loss of the inhibitory effect of prostacyclin on the stimulation of thrombin generation was due to the loss of platelet high-affinity prostanoid receptors, which may contribute to atherogenesis in individuals with chronic SCI.
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页码:245 / 249
页数:5
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