Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness - PubMed (original) (raw)
Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness
S AbdAlla et al. Nat Med. 2001 Sep.
Abstract
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.
Comment in
- Receptor double-trouble in preeclampsia.
Lodwick D. Lodwick D. Nat Med. 2001 Sep;7(9):999-1000. doi: 10.1038/nm0901-999. Nat Med. 2001. PMID: 11533700 No abstract available.
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