AbdAlla S, Lother H, el Massiery A, Quitterer U
Medical Research Center, Ain Champs University Hospital, Cairo, Egypt.
Nat Med. 2001 Sep;7(9):1003-9. doi: 10.1038/nm0901-1003.
Several examples of functional G-protein-coupled receptor heterodimers have been identified. However, it is not known whether receptor heterodimerization is involved in the pathogenesis of human disorders. Here we show that in preeclamptic hypertensive women, a significant increase in heterodimerization occurs between the AT(1)-receptor for the vasopressor angiotensin II and the B(2)-receptor for the vasodepressor bradykinin. AT(1)-B(2)-receptor heterodimerization in preeclampsia correlated with a 4-5-fold increase in B(2)-receptor protein levels. Expression of the AT(1)-B(2) heterodimer increased the responsiveness to angiotensin II and conferred resistance in AT(1)-receptors to inactivation by reactive oxygen species raised in normotensive and preeclamptic pregnancies. We suggest that AT(1)-B(2) heterodimers contribute to angiotensin II hypersensitivity in preeclampsia. Moreover, we identify preeclampsia as the first disorder associated with altered G-protein-coupled receptor heterodimerization.
已经鉴定出几种功能性G蛋白偶联受体异二聚体的实例。然而，尚不清楚受体异二聚化是否参与人类疾病的发病机制。在此我们表明，在子痫前期高血压女性中，血管升压素血管紧张素II的AT(1)受体与血管降压素缓激肽的B(2)受体之间的异二聚化显著增加。子痫前期中AT(1)-B(2)受体异二聚化与B(2)受体蛋白水平增加4-5倍相关。AT(1)-B(2)异二聚体的表达增加了对血管紧张素II的反应性，并使AT(1)受体对正常血压和子痫前期妊娠中产生的活性氧失活具有抗性。我们认为AT(1)-B(2)异二聚体促成了子痫前期中血管紧张素II的超敏反应。此外，我们将子痫前期确定为第一种与G蛋白偶联受体异二聚化改变相关的疾病。
