Table 1.
Angiotensin Receptors heteromerization and its functional consequences.
| Receptors | Model | Effect | Reference | ||
|---|---|---|---|---|---|
| AT1R | – | AT1R | Monocytes from patients with hypertension | Increased Ang II-dependent monocyte activation and adhesiveness | AbdAlla et al., 2004 |
| AT1R | – | APJR | Transfected CHO-K1 cells | Diminished Ang II binding to AT1R | Siddiquee et al., 2013 |
| AT1R | – | AT2R | Rat fetal fibroblast; human myometrial biopsies | Inhibition of inositol phosphate generation | AbdAlla et al., 2001 |
| AT1R | – | B2R | Transfected HEK293T cells | Ang II hypersensitivity | AbdAlla et al., 2000 |
| AT1R | – | B2R | Primary aortic VSMC | Blocked arrestin-dependent internalization of B2R | Wilson et al., 2013 |
| AT1R | – | B2R | Human placental biopsies | Increased calcium signaling and high vascular smooth muscle mechanosensitivity | Quitterer et al., 2019 |
| AT1R | – | CB1R | Hepatic stellate cells from rats | Enhanced calcium and mitogenic response to Ang II | Rozenfeld et al., 2011 |
| AT1R | – | CCR2 | Transfected HEK293T and subtotal-nephrectomized rat (chronic kidney disease model) |
Enhanced β-arrestin2 recruitment Renal injury |
Ayoub et al., 2015 |
| AT1R | – | D1R | Renal proximal tubule cells of WKY and SHR, A10 aortic vascular smooth muscle cells |
Decreased AT1R induced by D1R stimulation in WKY and SHR and A10 vascular smooth muscle cells Increased D1R induced by D1R stimulation only in WKY. D1R-AT1R interaction greater in WKY than in SHR D1R-AT1R interaction increased in WKY and decreased in SHR after D1R stimulation |
Zeng et al., 2003b |
| AT1R | – | D2R | Ethanol-administered rats | Attenuated calcium and mitogenic response to Ang II | Martinez-Pinilla et al., 2015 |
| AT1R | – | D3R | Renal proximal tubule cells of SHR and WKY |
Decreased D3R induced by Ang II in both strains, being greater in SHR than in WKY Decreased AT1R in WKY by Ang II Increased AT1R in SHR by Ang II |
Zeng et al., 2003a |
| AT1R | – | D5R | Renal proximal tubule cells of SHR and WKY |
Negatively regulation of the expression of each receptor. Decreased D5R expression induced by Ang II in WKY and SHR. |
Zeng et al., 2005b |
| AT1R | – | ETBR | Renal proximal tubule cells of SHR and WKY | Increased ETBR expression induced by Ang II in WKY cells. No change in SHR cells | Zeng et al., 2005a |
| AT1R | – | FP | Primary rat aortic VSMCs | Increased binding to AT1R | Goupil et al., 2015 |
| AT1R | – | MasR | Transfected HEK293T and mesenteric microvessels from wild type and MasR-KO mice | Decreased Ang II-induced production of inositol phosphates and mobilization of intracellular calcium | Kostenis et al., 2005 |
| AT1R | – | P2Y6R | VSMCs from mice | P2Y6 promotes Ang II–induced hypertension | Nishimura et al., 2016 |
| AT1R | – | SecR | Transfected CHO, HEK293T and COS-1 cells | Negative allosteric modulatory impact on secretin-stimulated cAMP responses at SecR; Positive allosteric modulatory impact on secretin-stimulated cAMP responses at AT1R | Harikumar et al., 2016 |
| AT1R | – | α1DR | Aortic tissue from healthy and preeclamptic pregnant rats | Higher heterodimerization in preeclamptic rats compared to control group | Gonzalez-Hernandez Mde et al., 2010 |
| AT1R | – | α2C-AR | Transfected HEK293T cells and mouse superior cervical ganglion neurons | Atypical Gs-PKA signaling and norepinephrine hypersecretion | Bellot et al., 2015 |
| AT1R | – | β2AR | Transfected COS-7 and HEK293T cells | Enhancement of β-arrestin coupling to β2AR | Toth et al., 2017 |
| AT1R | – | βAR | Mouse cardiomyocytes; HUVECs; transfected COS-7 and HEK293T cells | Crossinhibition of signaling coupled to each receptor | Barki-Harrington et al., 2003 |
| AT2R | – | AT2R | Mice model of Alzheimer disease | Gαq/11 sequestration and dysfunction | AbdAlla et al., 2009 |
| AT2R | – | B2R | Transfected PC-12 cells |
Enhancement of NO generation | Abadir et al., 2006 |
| AT2R | – | MasR | Cultured astrocytes from mice | Induced CX3CR1 mRNA expression | Leonhardt et al., 2017 |
| AT2R | – | MasR | Obese Zucker rat kidney |
Increased NO generation Diuretic and natriuretic responses |
Patel et al., 2017 |
| MasR | – | B2R | Transfected HEK293T cells |
Delayed sequestration of MasR from the plasma membrane Increased affinity ligand binding of MasR |
Cerrato et al., 2016 |
| MrgDR | – | MrgER | Transfected HEK293T cells |
Decreased MrgDR internalization Increased ERK1/2 phosphorylation |
Milasta et al., 2006 |
Ang II, Angiotensin II; APJR, apelin receptor; AT1R, Ang II receptor type 1; AT2R, Ang II receptor type 2; B2R, Bradykinin receptor type 2; cAMP, Cyclic adenosine monophosphate; CHO, Chinese hamster ovary; CX3CR1, CX3C chemokine receptor; D1R, dopamine receptor type 1; D2R, dopamine receptor type 2; D3R, dopamine receptor type 3; D4R, dopamine receptor type 4; D5R, dopamine receptor type 5; ETBR, Endothelin receptor type B; FPR, Prostaglandin F receptor; HEK293T, human embryonic kidney 293T; HUVECs, Human umbilical vein endothelial cells; KO, knockout; MrgDR, Mas-related G protein-coupled receptor member D receptor; MrgER, Mas-related G protein-coupled receptor member E receptor; NO, nitric oxide; P2Y6R, P2Y6 purinergic receptor; PKA, protein kinase A; SecR, secretin receptor; SERCA, sarco/endoplasmic reticulum Ca2+-ATPase; SHR, Spontaneously hypertensive rat; VSMC, Vascular smooth muscle cells; WKY, Wistar Kyoto; α1DR, adrenergic α1D receptor; α2C receptor; α2C-AR, adrenergic; β2AR, adrenergic β2 receptor; βAR, adrenergic β receptor.