Angiotensin-II Type 1 Receptor - AT1R

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Angiotensin-II Type 1 Receptor - AT1R

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Angiotensin-II Type 1 Receptor - AT1R
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Recent research has focused on the Angiotensin II Type I Receptor (AT1R) as a crucial component in diseases associated with COVID-19 (El-Arif et al., 2022). The AT1R activity is dependent on Gq/11.


El-Arif G, Khazaal S, Farhat A, Harb J, Annweiler C, Wu Y, Cao Z, Kovacic H, Abi Khattar Z, Fajloun Z, Sabatier JM - "Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases" Molecules 27(7):2048 (2022)

Wallukat G, Hohberger B, Wenzel K, Fürst J, Schulze-Rothe S, Wallukat A, Hönicke AS, Müller J - "Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms" J Transl Autoimmun 4:100100 (2021) ... MC8049853/
"Two of the identified GPCR-fAABs, observed in over 90% of the investigated COVID-19 patient sera (29/31), were directed against receptors of RAS, namely the angiotensin II AT1 receptor and the angiotensin (1–7) MAS receptor."

Heyman SN, Walther T, Abassi Z - "Angiotensin-(1-7)-A Potential Remedy for AKI: Insights Derived from the COVID-19 Pandemic" J Clin Med 10(6):1200. (2021)
"The COVID-19 disease is characterized by the depletion of ACE2 and Ang-(1-7), conceivably playing a central role in the devastating cytokine storm that characterizes this disorder."

Files DC, Gibbs KW, Schaich CL, Collins SP, Gwathmey TM, Casey JD, Self WH, Chappell MC - "A Pilot Study to Assess the Circulating Renin-Angiotensin-System in COVID-19 Acute Respiratory Failure" Am J Physiol Lung Cell Mol Physiol. 2021 May 19. doi: 10.1152/ajplung.00129.2021. Epub ahead of print. PMID: 34009036.


Oyagbemi AA, Adejumobi OA, Jarikre TA, Ajani OS, Asenuga ER, Gbadamosi IT, Adedapo ADA, Aro AO, Ogunpolu BS, Hassan FO, Falayi OO, Ogunmiluyi IO, Omobowale TO, Arojojoye OA, Ola-Davies OE, Saba AB, Adedapo AA, Emikpe BO, Oyeyemi MO, Nkadimeng SM, McGaw LJ, Kayoka-Kabongo PN, Oguntibeju OO, Yakubu MA - "Clofibrate, a Peroxisome Proliferator-Activated Receptor-Alpha (PPARα) Agonist, and Its Molecular Mechanisms of Action against Sodium Fluoride-Induced Toxicity" Biol Trace Elem Res 200(3):1220-1236 (2022)

Vasant RA, Khajuria MC, Narasimhacharya AV - "Antioxidant and ACE enhancing potential of Pankajakasthuri in fluoride toxicity: an in vitro study on mammalian lungs" Toxicol Ind Health 27(9):793-801 (2011)

Sakai H, Nishizawa Y, Nishimura A, Chiba Y, Goto K, Hanazaki M, Misawa M - "Angiotensin II induces hyperresponsiveness of bronchial smooth muscle via an activation of p42/44 ERK in rats" Pflugers Arch 460(3):645-55 (2010)

Jensen AM, Bae EH, Fenton RA, Nørregaard R, Nielsen S, Kim SW, Frøkiaer J - "Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction" Am J Physiol Renal Physiol 296(1):F127-34 (2009)

Sayeski PP, Ali MS, Bernstein KE - "The role of Ca2+ mobilization and heterotrimeric G protein activation in mediating tyrosine phosphorylation signaling patterns in vascular smooth muscle cells" Mol Cell Biochem 212(1-2):91-8. PMID: 11108140 (2000) (see also: Gq/11)


Cabana J, Holleran B, Leduc R, Escher E, Guillemette G, Lavigne P - "Identification of Distinct Conformations of the Angiotensin-II Type 1 Receptor Associated with the Gq/11 Protein Pathway and the β-Arrestin Pathway Using Molecular Dynamics Simulations" J Biol Chem 290(25):15835-15854 (2015) ... 20)35077-8

Philippe A, Kleinau G, Gruner JJ, Wu S, Postpieszala D, Speck D, Heidecke H, Dowell SJ, Riemekasten G, Hildebrand PW, Kamhieh-Milz J, Catar R, Szczepek M, Dragun D, Scheerer P - "Molecular Effects of Auto-Antibodies on Angiotensin II Type 1 Receptor Signaling and Cell Proliferation" Int J Mol Sci 23(7):3984 (2022)

Canals M, Jenkins L, Kellett E, Milligan G - "Up-regulation of the angiotensin II type 1 receptor by the MAS proto-oncogene is due to constitutive activation of Gq/G11 by MAS" J Biol Chem 281(24):16757-67 (2006)

Turu G, Várnai P, Gyombolai P, Szidonya L, Offertaler L, Bagdy G, Kunos G, Hunyady L - "Paracrine transactivation of the CB1 cannabinoid receptor by AT1 angiotensin and other Gq/11 protein-coupled receptors" J Biol Chem 284(25):16914-16921 (2009) ... MC2719328/[/list]

Hunyady L, Catt KJ - "Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II" Mol Endocrinol 20(5):953-70 (2006)
"Ang II-induced AT1R activation via Gq/11 stimulates phospholipases A2, C, and D, and activates inositol trisphosphate/Ca2+ signaling, protein kinase C isoforms, and MAPKs, as well as several tyrosine kinases (Pyk2, Src, Tyk2, FAK), scaffold proteins (G protein-coupled receptor kinase-interacting protein 1, p130Cas, paxillin, vinculin), receptor tyrosine kinases, and the nuclear factor-kappaB pathway."

Abe K, Nakashima H, Ishida M, Miho N, Sawano M, Soe NN, Kurabayashi M, Chayama K, Yoshizumi M, Ishida T - "Angiotensin II-induced osteopontin expression in vascular smooth muscle cells involves Gq/11, Ras, ERK, Src and Ets-1" Hypertens Res 31(5):987-98 (2008). doi: 10.1291/hypres.31.987.
"Ang II-induced OPN expression in VSMC is mediated by signaling cascades involving G(q/11) the Ras-ERK axis, and the Src kinase family, and by the transcription factor, Ets-1."

Cui Y, Kassmann M, Nickel S, Zhang C, Alenina N, Anistan YM, Schleifenbaum J, Bader M, Welsh DG, Huang Y, Gollasch M - "Myogenic Vasoconstriction Requires Canonical Gq/11 Signaling of the Angiotensin II Type 1 Receptor" J Am Heart Assoc 11(4):e022070 (2022)


Ang-II levels are increased in hypothyroidism and decreased in hyperthyroidism.

Carneiro-Ramos MS, Diniz GP, Almeida J, Vieira RL, Pinheiro SV, Santos RA, Barreto-Chaves ML - "Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism" J Physiol 583(Pt 1):213-23 (2007)

Segarra AB, Ramírez M, Banegas I, Hermoso F, Vargas F, Vives F, Alba F, de Gasparo M, Prieto I - "Influence of thyroid disorders on kidney angiotensinase activity" Horm Metab Res 38(1):48-52 (2006)

Figueroa-Vega N, Sanz-Cameno P, Moreno-Otero R, Sánchez-Madrid F, González-Amaro R, Marazuela M - "Serum levels of angiogenic molecules in autoimmune thyroid diseases and their correlation with laboratory and clinical features" J Clin Endocrinol Metab 94(4):1145-53 (2009)

Lee DS, Chung JK, Cho BY, Koh CS, Lee M - "Changes of serum angiotensin-converting enzyme activity during treatment of
patients with Graves' disease" Korean J Intern Med 1(1):104-12 (1986)

Czernobilsky H, Fiehn W, Ziegler R - "Comparison of serum angiotensin-converting enzyme in Graves' disease, toxic nodular goiter, and other thyroid conditions" Klin Wochenschr 63(11):518-22 (1985)

Nakamura Y, Takeda T, Ishii M, Nishiyama K, Yamakada M, Hirata Y, Kimura K, Murao S - "Elevation of serum angiotensin-converting enzyme activity in patients with hyperthyroidism" J Clin Endo Meta 55:931(1982)

Silverstein E, Schussler GC, Friedlang J - "Elevated serum angiotensin-converting enzyme in hyperthyroidism" Am J Med 75:233 (1983)

Yotsumoto H, Imai Y, Kuzuya N, Uchimura H, Matsuzaki F - "Increased levels of serum angiotensin-converting activity in hyperthyroidism" Am J Med 75:233 (1983)
"However, the action of thyroid hormones on angiotensin receptors is tissue-dependent. AII receptors in atrium, thoracic aortic, and liver tissues were increased in experimental hyperthyroidism in dogs (Sernia et al. 1993), similar to the findings by Marchant et al. (1993) in hyperthyroid rats, in which AII receptors were increased in the heart, liver, and kidneys but reduced in the adrenal gland." (Vargas et al., 2012)

Vargas F, Rodríguez-Gómez I, Vargas-Tendero P, Jimenez E, Montiel M - "The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations" J Endocrinol 213(1):25-36 (2012)
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