Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness.
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.
AbdAlla
S
S
Medical Research Center, Ain Champs University Hospital, Cairo, Egypt.
Lother
H
H
el Massiery
A
A
Quitterer
U
U
D000328:Adult; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D019281:Dimerization; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D009852:Omentum / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000378:metabolism*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction
D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D000804:Angiotensin II; D019204:GTP-Binding Proteins