Prostacyclin analogs stimulate receptor-mediated cAMP synthesis and ATP release from rabbit and human erythrocytes.

Prostacyclin analogs stimulate receptor-mediated cAMP synthesis and ATP release from rabbit and human erythrocytes.
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DOI:
10.1080/10739680701833804
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发表时间:
2008-07
期刊:
Microcirculation (New York, N.Y. : 1994)
影响因子:
--
通讯作者:
Stephenson AH
Stephenson AH
中科院分区:
其他
文献类型:
--
作者:
Sprague RS;Bowles EA;Hanson MS;DuFaux EA;Sridharan M;Adderley S;Ellsworth ML;Stephenson AH

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本研究的目的是确定前列腺环素(PGI2)受体(IP受体)存在于兔和人红细胞中,其激活刺激cAMP合成和ATP释放。在不存在和不存在IP受体拮抗剂CAY10441的情况下,测定红细胞与活性PGI2类似物伊洛prost或UT-15C孵育对cAMP水平和ATP释放的影响。Western分析法用于测定分离膜上IP受体的存在。为了确定PGI2类似物的作用不是由于前列腺素E2 (PGE2)受体激活,我们测定了PGE2对cAMP水平和ATP释放的影响。兔和人红细胞具有IP受体。Iloprost和UT-15C刺激了cAMP和ATP释放的增加,而这被IP受体拮抗剂CAY10441所阻止。PGE2不刺激cAMP积累或ATP释放,也不抑制伊洛前列素诱导的cAMP升高。本研究证实,IP受体存在于兔和人红细胞中,其激活导致cAMP和ATP释放增加。这些结果表明PGI2及其活性类似物在药理学上可以产生血管舒张的新机制。
The purpose of this study was to establish that the prostacyclin (PGI2) receptor (IP receptor) is present on rabbit and human erythrocytes and that its activation stimulates cAMP synthesis and ATP release. The effect of incubation of erythrocytes with the active PGI2 analogues, iloprost or UT-15C, on cAMP levels and ATP release was determined in the absence and presence of the IP receptor antagonist, CAY10441. Western analysis was used to determine the presence of the IP receptor on isolated membranes. To establish that effects of PGI2 analogues were not due to prostaglandin E2 (PGE2) receptor activation, the effect of PGE2 on cAMP levels and ATP release was determined. Rabbit and human erythrocytes possess IP receptors. Iloprost and UT-15C stimulated increases in cAMP and ATP release that were prevented by the IP receptor antagonist, CAY10441. PGE2 did not stimulate cAMP accumulation or ATP release and did not inhibit iloprost-induced increases in cAMP. This study establishes that the IP preceptor is present on rabbit and human erythrocytes and that its activation results in increases in cAMP and ATP release. These results suggest a novel mechanism by which PGI2 and its active analogues, when administered pharmacologically, could produce vasodilation.
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