Molecular Characterization of a Dual Endothelin-1/Angiotensin II Receptor

Ruiz-Opazo, Nelson; Hirayama, Kenji; Akimoto, Kaoru; Herrera, Victoria L. M.

doi:10.1007/bf03401733

Cited by 33 publications

(29 citation statements)

References 40 publications

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“…DQ009865). RNA blot analysis was done as described (43), using PolyAϩ RNA (3 g) and ␥-32 P end-labeled anti-sense mouse Dear oligonucleotide (5Ј-AGTGATAGAGCCCCAGTTCCAGCGAGACTTCATCTCCT-TGC-3Ј) as probe. Receptor expression studies with 125 I-ET-1 and 125 I-ANG II binding to membranes were done as described (28 Targeted disruption of Dear in mice.…”

Section: Methodsmentioning

confidence: 99%

“…We began antibody treatments 6 wk after irradiation at 12 wk of age. We used affinitypurified rabbit IgG anti-Dear anti-peptide antibody raised against the synthetic peptide P 51LLTSLGSKE60 (43). As control, we used rabbit IgG (sc-2027; Santa Cruz Biologicals, Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

“…1), thus allowing comparative analysis to published knockout mouse models of ET-1, ANG II, and their respective multiple receptors. Molecular characterization of mouse Dear genomic clone detects a one-exon transcription unit showing 78% amino acid sequence homology with the rat receptor (43) (Fig. 1A).…”

Section: Characterization Of Mouse Dear and Development Of Deardeficimentioning

confidence: 99%

“…Likewise, of the three single-ligand ANG II receptors that have been characterized, AT1 A , AT1 B , and AT-2 receptors, AT1 A underlies ANG IIstimulated angiogenesis in tumors (18), whereas AT 2 receptor negatively modulates ischemia-induced angiogenesis (50). Standing apart, however, is the dual ET-1/ANG II receptor (Dear), which binds ET-1 and ANG II with equal affinities in the rat (43). Dear responds to ET-1 and ET-2 but minimally to , just like the ET A receptor.…”

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confidence: 99%

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Embryonic lethality inDeargene-deficient mice: new player in angiogenesis

Herrera

Ponce

Bagamasbad

et al. 2005

Physiological Genomics

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The dual endothelin-1/ angiotensin II receptor (Dear) binds endothelin-1 (ET-1) and angiotensin II (ANG II) with equal affinities in the Dahl S/JR HS rat strain. To elucidate its physiological significance within the context of multiple receptor isoforms and diverse ET-1 and ANG II functions spanning blood pressure regulation, tumor proliferation, and angiogenesis, we characterized mouse Dear and Dear-deficient mice. Unlike null mutant models of ET-1, ANG II, and all other ET-1 and ANG II receptors, Dear Ϫ/Ϫ deficiency results in impaired angiogenesis, dysregulated neuroepithelial development, and embryonic lethality by embryonic day 12.5. Interestingly, mouse Dear does not bind ANG II, similar to Dahl R/JR HS rat Dear, but binds ET-1 and vascular endothelial growth factor (VEGF) signal peptide (VEGFsp) with equal affinities, suggesting a putative novel multifunction for VEGFsp and a parsimonious mechanism for coordination of VEGF-induced and Dear-mediated pathways. Consistent with its developmental angiogenic role, Dear inhibition results in decreased tumor growth in B16-F10 melanoma cell-induced subcutaneous tumor in female Dear ϩ/Ϫ /C57BL6 BC10 mice, but not in males (age 3.5 mo), and in 127 Cs radiation-induced orthotopic mammary tumors in SpragueDawley female rats (age range 3-6.5 mo). Altogether, the data identify Dear as a new player in angiogenesis during development downstream to, and nonredundant with, VEGF-mediated pathways, as well as a putative modulator of tumor angiogenesis acting within a gender-specific paradigm.endothelin-1 receptor; VEGF signal peptide; vascular development; neuroepithelial development; cardiac development VASCULAR NETWORK DEVELOPMENT, or vascularization, is a complex process whose key component paradigms, vasculogenesis, angiogenesis, and vascular remodeling, comprise interacting pathways involving or modulating vascular endothelial growth factor (VEGF)-A and its isoforms VEGF 121 , VEGF 165 , and VEGF 189 ; angiopoietins 1 and 2 and their respective receptor tyrosine kinases; flk-1 or VEGFR2 receptor; and Tie2 or angiopoeitin receptor (40). As with other processes, normal vascular development pathways are recruited into pathological pathways, producing a spectrum of pathological angiogenesis as seen in solid tumors, arthritis, and diabetes. While VEGF is a key regulator of vascularization in health and disease (7), the complexity of vascularization is nevertheless evident, as other key modulators of angiogenesis, defined by embryonic lethal phenotypes associated with abnormal embryonic and/or extraembryonic vascularization phenotypes, exist. These modulators represent diverse functional groups, such as transcription factors like hypoxia-inducible transcription factor (45) and HAND1 (34), energy metabolism regulators like Foxo1 (19), ion pumps like Na/Ca exchanger (9), integrins like ␤8 (58) and ␣7/␤1 integrin (17) and regulators of integrins like focal adhesion kinase (49), growth factors like transforming growth factor (TGF)-␤1 (31), signal transduction kinases like p38␣ mi...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Characterization Of Mouse Dear and Development Of Deardeficimentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Embryonic lethality inDeargene-deficient mice: new player in angiogenesis

Herrera

Ponce

Bagamasbad

et al. 2005

Physiological Genomics

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“…6,9 There is also a report of a novel, transmembrane receptor that contains distinct ET and Ang II binding sites, although whether this has any functional role is unclear. 12 Finally, it is evident that ET and Ang II signal through several common intracellular pathways. 2,3,13 The introduction and use of ET A and ET B receptor antagonists have allowed further investigation into the actions of ET and its interactions with Ang II.…”

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confidence: 99%

Endothelin Mediates Some of the Renal Actions of Acutely Administered Angiotensin II

2001

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Abstract-Recent studies suggest that endogenous endothelin mediates much of the vasoconstrictor activity and vascular fibrotic damage caused by chronic administration of angiotensin II. The present study uses the mixed endothelin-A and endothelin-B receptor antagonist bosentan and the endothelin-A-selective blocker BQ-123 to study the contribution of endogenous endothelin to the pressor and renal action of acutely administered angiotensin II in conscious, chronically catheterized rats. Exposure to angiotensin II at 0.48 pmol 0.5 ng/100 g body weight per min IV (low dose) and 1.91 pmol 2.0 ng/100 g body weight per min IV (high dose) raised mean arterial blood pressure (18Ϯ4 mm Hg, PϽ0.01, and 39Ϯ4 mm Hg, PϽ0.005, respectively) while also increasing renal vascular resistance (4.3Ϯ1 mm Hg/mL per min, PϽ0.001, and 10Ϯ1 mm Hg/mL per min, PϽ0.001, respectively). In the presence of bosentan, pressor and renal vasoconstrictor responses to low-dose angiotensin II were blunted (PϽ0.02 and PϽ0.01, respectively), and the results with BQ-123 were similar. In contrast, these parameters were unaffected during high-dose angiotensin II infusionϩbosentan, although BQ-123 did selectively reduce the rise in renal vascular resistance, possibly via an endothelin B-mediated nitric oxide effect. In contrast, high-dose angiotensin II caused natriuretic and diuretic effects that were completely prevented by bosentan. These results show that endothelin (via endothelin A) contributes to the pressor and renal vasoconstrictor actions of acutely administered low-dose angiotensin II. Furthermore, our data suggest that the previously described angiotensin II-induced natriuresis and diuresis observed with a high pressor dose of angiotensin II is mediated by endothelin. Key Words: vascular resistance Ⅲ glomerular filtration rate Ⅲ natriuresis Ⅲ rats Ⅲ angiotensin II A ngiotensin II (Ang II) is a potent endogenous vasoconstrictor that, when activated, produces increases in blood pressure (BP) and renal vasoconstriction and stimulates cell growth. 1,2 Most of these actions of Ang II are mediated by activation of the angiotensin type 1 (AT 1 ) receptor, 2 and many of these actions resemble those of another potent endogenous vasoconstrictor, endothelin (ET). Two ET receptor subtypes have been characterized, and activation of ET type A (ET A ) receptors on vascular smooth muscle (VSM) causes vasoconstriction and proliferation of cells. ET type B (ET B ) receptors are expressed on endothelial cells, in which they cause relaxation of adjacent VSM via nitric oxide and prostacyclin release, and on VSM, in which they cause vasoconstriction. 3 Acutely administered ET produces a transient ET B -mediated hypotension, followed by a prolonged hypertension and renal vasoconstriction with consequent decreases in renal blood flow and glomerular filtration rate (GFR) in conscious rats. 4 Ang II and ET can interact at several levels. Administered ET has a synergistic effect to augment the pressor actions of Ang II. 5 The hypertension and renal vasoconstriction produ...

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Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review

Root‐Bernstein¹

2005

J. Mol. Recognit.

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This paper reviews the three major theories of peptide receptor evolution: (1) Dwyer's theory that peptide receptors evolved from self-aggregating peptides; (2) Root-Bernstein's theory that peptide receptors evolved from functionally and structurally complementary peptides; and (3) Blalock's theory that receptors evolved from hydropathically complementary sequences encoded in the antisense strand of the DNA encoding each peptide. The evidence to date suggests that the co-yevolution of peptides and their receptors is strongly constrained by one or more of these physicochemically based mechanisms, which argues against a random or frozen accident' model. The data also suggest that structure and function are integrally related from the earliest steps of receptor-ligand evolution so that peptide functionality is non-random and highly conserved in its origin. The result is a molecular paleontology' that reveals the evolutionary constraints that shaped the interaction of structure and function.

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Molecular Characterization of a Dual Endothelin-1/Angiotensin II Receptor

Cited by 33 publications

References 40 publications

Embryonic lethality inDeargene-deficient mice: new player in angiogenesis

Embryonic lethality inDeargene-deficient mice: new player in angiogenesis

Endothelin Mediates Some of the Renal Actions of Acutely Administered Angiotensin II

Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review

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