Okwu A K, Ullian M E, Halushka P V
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston.
J Pharmacol Exp Ther. 1992 Jul;262(1):238-45.
Desensitization of platelet thromboxane (TX)A2/prostaglandin (PG)H2 receptors was induced by incubating platelet-rich plasma with the stable PGH2 analog 11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619) (1 microM). Iloprost, a stable prostacyclin analog, was included in the incubation to prevent platelet activation. The TXA2 mimetic, [1S-1 alpha,2 beta(5Z), 3 alpha(1E,3S*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo - [2.2.1]heptan-2-yl]-5-heptenoic acid (I-BOP), was used to induce platelet aggregation, shape change and increases in intracellular free calcium. The EC50 values for I-BOP-induced rise in intracellular free calcium (control = 10.2 +/- 1.5 nM; desensitized = 79.4 +/- 22.4 nM, n = 6, P less than .05), aggregation (control = 15.8 +/- 2.4 nM; desensitized = 51.7 +/- 11.9 nM; P less than .05, n = 5) and shape change (control = 172 +/- 37 pM; desensitized = 350 +/- 60 pM; P less than .05, n = 7) were increased by the preincubation with U46619. Aggregation responses to thrombin and the calcium ionophore, ionomycin, were unaltered by the preincubation with U46619. Equilibrium binding studies at pH 7.4 revealed a decrease in the number of binding sites for the receptor antagonist 9,11-dimethylmethano-11,12- methano-16(3-iodo-4-hydroxyphenyl)-13,14-dihydro-13-aza-15 alpha beta-omega- tetranor-TXA2 [125I]PTA-OH) (control = 3246 +/- 509 sites/platelet, desensitized = 2198 +/- 324 sites/platelet, n = 6, P less than .05) without a change in affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
通过将富含血小板的血浆与稳定的前列腺素H2类似物11α,9α-(环氧亚甲基)前列腺-5Z,13E-二烯酸（U46619）（1微摩尔）一起孵育，诱导血小板血栓素（TX）A2/前列腺素（PG）H2受体脱敏。孵育过程中加入稳定的前列环素类似物伊洛前列素以防止血小板活化。使用TX A2模拟物[1S-1α,2β(5Z), 3α(1E,3S*), 4α]-7-[3-(3-羟基-4-(4'-碘苯氧基)-1-丁烯基)-7-氧杂双环-[2.2.1]庚烷-2-基]-5-庚烯酸（I-BOP）诱导血小板聚集、形态变化和细胞内游离钙增加。I-BOP诱导的细胞内游离钙升高（对照组=10.2±1.5纳摩尔；脱敏组=79.4±22.4纳摩尔，n=6，P<0.05）、聚集（对照组=15.8±2.4纳摩尔；脱敏组=51.7±11.9纳摩尔；P<0.05，n=5）和形态变化（对照组=172±37皮摩尔；脱敏组=350±60皮摩尔；P<0.05，n=7）的半数有效浓度（EC50）值因预先与U46619孵育而升高。预先与U46619孵育对凝血酶和钙离子载体离子霉素的聚集反应无影响。在pH 7.4条件下的平衡结合研究显示，受体拮抗剂9,11-二甲基亚甲基-11,12-亚甲基-16(3-碘-4-羟基苯基)-13,14-二氢-13-氮杂-15αβ-ω-四去甲-TX A2[125I]PTA-OH的结合位点数量减少（对照组=3246±509个位点/血小板，脱敏组=2198±324个位点/血小板，n=6，P<0.05），而亲和力无变化。（摘要截断于250字）
