精氨酸加压素及其受体的结构与功能研究进展
Research Progress on the Structure and Function of Arginine Vasopressin and Its Receptor
DOI: 10.12677/hjbm.2025.152040, PDF,   
作者: 姚菊霞, 尹万超：中国科学院上海药物研究所，上海；中国科学院大学，北京
关键词: 精氨酸加压素；V1a受体；V1b受体；V2受体；结构与功能分析；Arginine Vasopressin； V1aR； V1bR； V2R； Structural and Functional Analysis
摘要: 精氨酸加压素(Arginine Vasopressin, AVP)，又称抗利尿激素(Antidiuretic Hormone, ADH)，是一种由下丘脑合成的环状九肽神经激素，在机体水盐平衡和血压稳态调节中发挥核心调控作用。AVP通过特异性结合G蛋白偶联受体(G Protein-Coupled Receptor, GPCR)家族成员V1受体(Vasopressin type 1 receptor, V1R)和V2受体(Vasopressin type 2 receptor, V2R)介导其生理功能：V1R主要分布于血管平滑肌，参与调控血管张力及血小板活化；V2R则高表达于肾脏集合管和远端肾小管，通过调节水通道蛋白2 (Aquaporin-2, AQP2)的膜转运介导水的重吸收。近年来，随着冷冻电子显微镜(Cryogenic Electron Microscopy, Cryo-EM)等结构生物学技术的突破，研究人员成功解析了AVP受体复合物的高分辨率三维结构，为阐明其配体识别机制和信号转导途径提供了重要的结构基础。这些研究成果不仅深化了对AVP信号通路的分子机制理解，也为基于结构的精准药物设计提供了新思路。基于V1R和V2R结构特征开发的高选择性配体有望为高血压、尿崩症等疾病的治疗提供更安全有效的治疗方案。
Abstract: Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is a cyclic nonapeptide neurohormone synthesized in the hypothalamus, playing a critical role in maintaining water-electrolyte balance and blood pressure homeostasis. AVP mediates its effects through specific binding to G protein-coupled receptors (GPCRs), primarily V1R and V2R. V1R is predominantly expressed in vascular smooth muscle, where it regulates vascular tone and platelet activation, V2R is highly expressed in the renal collecting ducts and distal nephron, where V2R orchestrates water reabsorption by modulating the membrane trafficking of aquaporin-2 (AQP2). In recent years, with the breakthroughs in structural biology techniques such as Cryogenic Electron Microscopy (Cryo-EM), researchers have successfully determined the high-resolution three-dimensional structure of the arginine vasopressin (AVP) receptor complex. This achievement provides a crucial structural foundation for elucidating the ligand recognition mechanism and signal transduction pathway of the AVP receptor. These research findings not only deepen our understanding of the molecular mechanisms underlying the AVP signaling pathway but also offer novel insights into structure-based precision drug design. Highly selective ligands developed based on the structural characteristics of V1R (vasopressin receptor 1) and V2R (vasopressin receptor 2) hold great promise for providing safer and more effective therapeutic strategies for diseases such as hypertension and diabetes insipidus.
文章引用：姚菊霞, 尹万超. 精氨酸加压素及其受体的结构与功能研究进展[J]. 生物医学, 2025, 15(2): 339-349. https://doi.org/10.12677/hjbm.2025.152040

参考文献

[1] Yoshimura, M., Conway-Campbell, B. and Ueta, Y. (2021) Arginine Vasopressin: Direct and Indirect Action on Metabolism. Peptides, 142, Article ID: 170555. [Google Scholar] [CrossRef] [PubMed]
[2] Sato-Numata, K., Numata, T., Ueta, Y. and Okada, Y. (2021) Vasopressin Neurons Respond to Hyperosmotic Stimulation with Regulatory Volume Increase and Secretory Volume Decrease by Activating Ion Transporters and Ca2+ Channels. Cellular Physiology & Biochemistry, 55, 119-134. [Google Scholar] [CrossRef] [PubMed]
[3] Morris, M. and Alexander, N. (1989) Baroreceptor Influences on Oxytocin and Vasopressin Secretion. Hypertension, 13, 110-114.
[4] Grinevich, V. and Ludwig, M. (2021) The Multiple Faces of the Oxytocin and Vasopressin Systems in the Brain. Journal of Neuroendocrinology, 33, e13004. [Google Scholar] [CrossRef] [PubMed]
[5] Bankir, L., Guerrot, D. and Bichet, D.G. (2021) Vaptans or Voluntary Increased Hydration to Protect the Kidney: How Do They Compare? Nephrology Dialysis Transplantation, 38, 562-574. [Google Scholar] [CrossRef] [PubMed]
[6] Ghanavati, P.M., Khazaeli, D. and Amjadzadeh, M. (2021) A Comparison of the Efficacy and Tolerability of Treating Primary Nocturnal Enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin Alone: A Randomized Controlled Clinical Trial. International braz j urol, 47, 73-81. [Google Scholar] [CrossRef] [PubMed]
[7] Schrier, R.W., Gross, P., Gheorghiade, M., Berl, T., Verbalis, J.G., Czerwiec, F.S., et al. (2006) Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia. New England Journal of Medicine, 355, 2099-2112. [Google Scholar] [CrossRef] [PubMed]
[8] Policarpo, M., Baldwin, M.W., Casane, D. and Salzburger, W. (2024) Diversity and Evolution of the Vertebrate Chemoreceptor Gene Repertoire. Nature Communications, 15, Article No. 1421. [Google Scholar] [CrossRef] [PubMed]
[9] Liu, H., Zhong, H., Zhang, Y., Xue, H., Zhang, Z., Fu, K., et al. (2024) Structural Basis of Tolvaptan Binding to the Vasopressin V2 Receptor. Acta Pharmacologica Sinica, 45, 2441-2449. [Google Scholar] [CrossRef] [PubMed]
[10] He, Q., Xiao, P., Huang, S., Jia, Y., Zhu, Z., Lin, J., et al. (2021) Structural Studies of Phosphorylation-Dependent Interactions between the V2R Receptor and Arrestin-2. Nature Communications, 12, Article No. 2396. [Google Scholar] [CrossRef] [PubMed]
[11] Bous, J., Fouillen, A., Orcel, H., Trapani, S., Cong, X., Fontanel, S., et al. (2022) Structure of the Vasopressin Hormone-V2 Receptor-β-Arrestin1 Ternary Complex. Science Advances, 8, eabo7761. [Google Scholar] [CrossRef] [PubMed]
[12] Wang, L., Xu, J., Cao, S., Sun, D., Liu, H., Lu, Q., et al. (2021) Cryo-EM Structure of the AVP-Vasopressin Receptor 2-GS Signaling Complex. Cell Research, 31, 932-934. [Google Scholar] [CrossRef] [PubMed]
[13] Zhou, F., Ye, C., Ma, X., Yin, W., Croll, T.I., Zhou, Q., et al. (2021) Molecular Basis of Ligand Recognition and Activation of Human V2 Vasopressin Receptor. Cell Research, 31, 929-931. [Google Scholar] [CrossRef] [PubMed]
[14] Fujiwara, Y., Tanoue, A., Tsujimoto, G. and Koshimizu, T. (2011) The Roles of V1a Vasopressin Receptors in Blood Pressure Homeostasis: A Review of Studies on V1a Receptor Knockout Mice. Clinical and Experimental Nephrology, 16, 30-34. [Google Scholar] [CrossRef] [PubMed]
[15] Brands, J., Bravo, S., Jürgenliemke, L., Grätz, L., Schihada, H., Frechen, F., et al. (2024) A Molecular Mechanism to Diversify Ca2+ Signaling Downstream of GS Protein-Coupled Receptors. Nature Communications, 15, Article No. 7684. [Google Scholar] [CrossRef] [PubMed]
[16] Umemori, H., Inoue, T., Kume, S., Sekiyama, N., Nagao, M., Itoh, H., et al. (1997) Activation of the G Protein Gq/11 through Tyrosine Phosphorylation of the α Subunit. Science, 276, 1878-1881. [Google Scholar] [CrossRef] [PubMed]
[17] Murasawa, S., Matsubara, H., Kizima, K., Maruyama, K., Mori, Y. and Inada, M. (1995) Glucocorticoids Regulate V1a Vasopressin Receptor Expression by Increasing mRNA Stability in Vascular Smooth Muscle Cells. Hypertension, 26, 665-669. [Google Scholar] [CrossRef] [PubMed]
[18] Szczepanska-Sadowska, E., Czarzasta, K., Bogacki-Rychlik, W. and Kowara, M. (2024) The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases. International Journal of Molecular Sciences, 25, Article 7394.
[19] Carter, C.S. (2017) The Oxytocin-Vasopressin Pathway in the Context of Love and Fear. Frontiers in Endocrinology, 8, Article 356. [Google Scholar] [CrossRef] [PubMed]
[20] Tsuchiya, H., Fujimura, S., Fujiwara, Y. and Koshimizu, T.A. (2020) Critical Role of V1a Vasopressin Receptor in Murine Parturition. Biology of Reproduction, 102, 923-934. [Google Scholar] [CrossRef] [PubMed]
[21] Perrier, E.T., Armstrong, L.E., Bottin, J.H., Clark, W.F., Dolci, A., Guelinckx, I., et al. (2021) Hydration for Health Hypothesis: A Narrative Review of Supporting Evidence. European Journal of Nutrition, 60, 1167-1180.
[22] Ślusarz, M.J. (2024) Structural Basis for Antagonist Binding to Vasopressin V1b Receptor Revealed by the Molecular Dynamics Simulations. Biopolymers, 116, e23627. [Google Scholar] [CrossRef] [PubMed]
[23] Tanoue, A., Ito, S., Honda, K., Oshikawa, S., Kitagawa, Y., Koshimizu, T., et al. (2004) The Vasopressin V1b Receptor Critically Regulates Hypothalamic-Pituitary-Adrenal Axis Activity under Both Stress and Resting Conditions. Journal of Clinical Investigation, 113, 302-309. [Google Scholar] [CrossRef] [PubMed]
[24] Iob, E., Kirschbaum, C. and Steptoe, A. (2019) Persistent Depressive Symptoms, HPA-Axis Hyperactivity, and Inflammation: The Role of Cognitive-Affective and Somatic Symptoms. Molecular Psychiatry, 25, 1130-1140. [Google Scholar] [CrossRef] [PubMed]
[25] Török, B., Fazekas, C.L., Szabó, A. and Zelena, D. (2021) Epigenetic Modulation of Vasopressin Expression in Health and Disease. International Journal of Molecular Sciences, 22, Article 9415. [Google Scholar] [CrossRef] [PubMed]
[26] Erdélyi, L.S., Hunyady, L. and Balla, A. (2023) V2 Vasopressin Receptor Mutations: Future Personalized Therapy Based on Individual Molecular Biology. Frontiers in Endocrinology, 14, Article 1173601. [Google Scholar] [CrossRef] [PubMed]
[27] Wang, L., Guo, W., Fang, C., Feng, W., Huang, Y., Zhang, X., et al. (2021) Functional Characterization of a Loss-Of-Function Mutant I324M of Arginine Vasopressin Receptor 2 in X-Linked Nephrogenic Diabetes Insipidus. Scientific Reports, 11, Article No. 11057. [Google Scholar] [CrossRef] [PubMed]
[28] Felline, A., Bellucci, L., Vezzi, V., Ambrosio, C., Cotecchia, S. and Fanelli, F. (2024) Structural Plasticity of Arrestin-G Protein Coupled Receptor Complexes as a Molecular Determinant of Signaling. International Journal of Biological Macromolecules, 283, Article ID: 137217. [Google Scholar] [CrossRef] [PubMed]
[29] Xiang, Y. and Hwa, J. (2016) Regulation of VWF Expression, and Secretion in Health and Disease. Current Opinion in Hematology, 23, 288-293. [Google Scholar] [CrossRef] [PubMed]
[30] Gal, C.S. (2001) An Overview of SR121463, a Selective Non‐Peptide Vasopressin V2 Receptor Antagonist. Cardiovascular Drug Reviews, 19, 201-214. [Google Scholar] [CrossRef] [PubMed]
[31] Ranieri, M., Di Mise, A., Tamma, G. and Valenti, G. (2019) Vasopressin-Aquaporin-2 Pathway: Recent Advances in Understanding Water Balance Disorders. F1000Research, 8, Article 149. [Google Scholar] [CrossRef] [PubMed]
[32] Noda, Y., Horikawa, S., Kanda, E., Yamashita, M., Meng, H., Eto, K., et al. (2008) Reciprocal Interaction with G-Actin and Tropomyosin Is Essential for Aquaporin-2 Trafficking. The Journal of Cell Biology, 182, 587-601. [Google Scholar] [CrossRef] [PubMed]
[33] Lozić, M., Šarenac, O., Murphy, D. and Japundžić-Žigon, N. (2018) Vasopressin, Central Autonomic Control and Blood Pressure Regulation. Current Hypertension Reports, 20, Article No. 11. [Google Scholar] [CrossRef] [PubMed]
[34] Wasilewski, M.A., Grisanti, L.A., Song, J., Carter, R.L., Repas, A.A., Myers, V.D., et al. (2016) Vasopressin Type 1A Receptor Deletion Enhances Cardiac Contractility, β-Adrenergic Receptor Sensitivity and Acute Cardiac Injury-Induced Dysfunction. Clinical Science, 130, 2017-2027. [Google Scholar] [CrossRef] [PubMed]
[35] Pickett, J.R., Wu, Y., Zacchi, L.F. and Ta, H.T. (2023) Targeting Endothelial Vascular Cell Adhesion Molecule-1 in Atherosclerosis: Drug Discovery and Development of Vascular Cell Adhesion Molecule-1-Directed Novel Therapeutics. Cardiovascular Research, 119, 2278-2293. [Google Scholar] [CrossRef] [PubMed]
[36] Rabow, S., Jonsson, H., Bro, E. and Olofsson, P. (2023) Cardiovascular Effects of Oxytocin and Carbetocin at Cesarean Section. A Prospective Double-Blind Randomized Study Using Noninvasive Pulse Wave Analysis. The Journal of Maternal-Fetal & Neonatal Medicine, 36, Article ID: 2208252. [Google Scholar] [CrossRef] [PubMed]
[37] Li, X., Du, Y., Han, X., Wang, H., Sheng, Y., Lian, F., et al. (2023) Efficacy of Atosiban for Repeated Implantation Failure in Frozen Embryo Transfer Cycles. Scientific Reports, 13, Article No. 9277. [Google Scholar] [CrossRef] [PubMed]
[38] Torres, V.E. (2009) Vasopressin in Chronic Kidney Disease: An Elephant in the Room? Kidney International, 76, 925-928. [Google Scholar] [CrossRef] [PubMed]
[39] Piani, F., Reinicke, T., Lytvyn, Y., Melena, I., Lovblom, L.E., Lai, V., et al. (2021) Vasopressin Associated with Renal Vascular Resistance in Adults with Longstanding Type 1 Diabetes with and without Diabetic Kidney Disease. Journal of Diabetes and Its Complications, 35, Article ID: 107807. [Google Scholar] [CrossRef] [PubMed]
[40] Christ‐Crain, M., Winzeler, B. and Refardt, J. (2021) Diagnosis and Management of Diabetes Insipidus for the Internist: An Update. Journal of Internal Medicine, 290, 73-87. [Google Scholar] [CrossRef] [PubMed]
[41] Harada, K., Wada, E., Osuga, Y., Shimizu, K., Uenoyama, R., Hirai, M.Y., et al. (2025) Intestinal Butyric Acid-Mediated Disruption of Gut Hormone Secretion and Lipid Metabolism in Vasopressin Receptor-Deficient Mice. Molecular Metabolism, 91, Article ID: 102072. [Google Scholar] [CrossRef] [PubMed]
[42] Angelousi, A., Alexandraki, K.I., Mytareli, C., Grossman, A.B. and Kaltsas, G. (2023) New Developments and Concepts in the Diagnosis and Management of Diabetes Insipidus (AVP‐Deficiency and Resistance). Journal of Neuroendocrinology, 35, e13233. [Google Scholar] [CrossRef] [PubMed]
[43] Juruena, M.F., Eror, F., Cleare, A.J. and Young, A.H. (2020) The Role of Early Life Stress in HPA Axis and Anxiety. In: Kim, Y.K., Eds., Anxiety Disorders, Springer, 141-153. [Google Scholar] [CrossRef] [PubMed]
[44] Goutier, W., Kloeze, M. and McCreary, A.C. (2014) Nicotine‐Induced Locomotor Sensitization: Pharmacological Analyses with Candidate Smoking Cessation Aids. Addiction Biology, 21, 234-241. [Google Scholar] [CrossRef] [PubMed]
[45] Raff, H. and Carroll, T. (2015) Cushing’s Syndrome: From Physiological Principles to Diagnosis and Clinical Care. The Journal of Physiology, 593, 493-506. [Google Scholar] [CrossRef] [PubMed]
[46] Nakamura, K., Velho, G. and Bouby, N. (2017) Vasopressin and Metabolic Disorders: Translation from Experimental Models to Clinical Use. Journal of Internal Medicine, 282, 298-309. [Google Scholar] [CrossRef] [PubMed]
[47] Vanya, M., Szucs, S., Vetro, A. and Bartfai, G. (2017) The Potential Role of Oxytocin and Perinatal Factors in the Pathogenesis of Autism Spectrum Disorders—Review of the Literature. Psychiatry Research, 247, 288-290. [Google Scholar] [CrossRef] [PubMed]
[48] Rinschen, M.M., Schermer, B. and Benzing, T. (2014) Vasopressin-2 Receptor Signaling and Autosomal Dominant Polycystic Kidney Disease: From Bench to Bedside and Back Again. Journal of the American Society of Nephrology, 25, 1140-1147. [Google Scholar] [CrossRef] [PubMed]
[49] Prosperi, F., Suzumoto, Y., Marzuillo, P., Costanzo, V., Jelen, S., Iervolino, A., et al. (2020) Characterization of Five Novel Vasopressin V2 Receptor Mutants Causing Nephrogenic Diabetes Insipidus Reveals a Role of Tolvaptan for M272R-V2R Mutation. Scientific Reports, 10, Article No. 16383. [Google Scholar] [CrossRef] [PubMed]
[50] Fukuyama, S., Okudaira, S., Yamazato, S., Yamazato, M. and Ohta, T. (2003) Analysis of Renal Tubular Electrolyte Transporter Genes in Seven Patients with Hypokalemic Metabolic Alkalosis. Kidney International, 64, 808-816. [Google Scholar] [CrossRef] [PubMed]
[51] Hernandez, M., Sullivan, R.D., McCune, M.E., Reed, G.L. and Gladysheva, I.P. (2022) Sodium-Glucose Cotransporter-2 Inhibitors Improve Heart Failure with Reduced Ejection Fraction Outcomes by Reducing Edema and Congestion. Diagnostics, 12, Article 989. [Google Scholar] [CrossRef] [PubMed]
[52] Cataldo, I., Azhari, A. and Esposito, G. (2018) A Review of Oxytocin and Arginine-Vasopressin Receptors and Their Modulation of Autism Spectrum Disorder. Frontiers in Molecular Neuroscience, 11, Article 27. [Google Scholar] [CrossRef] [PubMed]
[53] Rigney, N., de Vries, G.J. and Petrulis, A. (2023) Modulation of Social Behavior by Distinct Vasopressin Sources. Frontiers in Endocrinology, 14, Article 1127792. [Google Scholar] [CrossRef] [PubMed]
[54] Verbalis, J.G. (2020) Acquired Forms of Central Diabetes Insipidus: Mechanisms of Disease. Best Practice & Research Clinical Endocrinology & Metabolism, 34, Article ID: 101449. [Google Scholar] [CrossRef] [PubMed]
[55] Leissinger, C., Carcao, M., Gill, J.C., Journeycake, J., Singleton, T. and Valentino, L. (2013) Desmopressin (DDAVP) in the Management of Patients with Congenital Bleeding Disorders. Haemophilia, 20, 158-167. [Google Scholar] [CrossRef] [PubMed]
[56] Brouard, R., Bossmar, T., Fournié‐Lloret, D., Chassard, D. and Åkerlund, M. (2000) Effect of SR49059, an Orally Active V1a Vasopressin Receptor Antagonist, in the Prevention of Dysmenorrhoea. BJOG: An International Journal of Obstetrics & Gynaecology, 107, 614-619. [Google Scholar] [CrossRef] [PubMed]
[57] Ponzoni, L., Braida, D., Bondiolotti, G. and Sala, M. (2017) The Non-Peptide Arginine-Vasopressin V1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish. Frontiers in Psychiatry, 8, Article 146. [Google Scholar] [CrossRef] [PubMed]
[58] Zhao, N., Peacock, S.O., Lo, C.H., Heidman, L.M., Rice, M.A., Fahrenholtz, C.D., et al. (2019) Arginine Vasopressin Receptor 1a Is a Therapeutic Target for Castration-Resistant Prostate Cancer. Science Translational Medicine, 11, eaaw4636. [Google Scholar] [CrossRef] [PubMed]
[59] Li-Ng, M. and Verbalis, J.G. (2010) Conivaptan: Evidence Supporting Its Therapeutic Use in Hyponatremia. Core Evi-dence, 4, 83-92. [Google Scholar] [CrossRef] [PubMed]
[60] Breshears, J.D., Jiang, B., Rowland, N.C., Kunwar, S. and Blevins, L.S. (2013) Use of Conivaptan for Management of Hyponatremia Following Surgery for Cushing’s Disease. Clinical Neurology and Neurosurgery, 115, 2358-2361. [Google Scholar] [CrossRef] [PubMed]
[61] Schnider, P., Bissantz, C., Bruns, A., Dolente, C., Goetschi, E., Jakob-Roetne, R., et al. (2020) Discovery of Balovaptan, a Vasopressin 1a Receptor Antagonist for the Treatment of Autism Spectrum Disorder. Journal of Medicinal Chemistry, 63, 1511-1525. [Google Scholar] [CrossRef] [PubMed]
[62] Pena, A., Murat, B., Trueba, M., Ventura, M.A., Bertrand, G., Cheng, L.L., et al. (2007) Pharmacological and Physiological Characterization of D[Leu4, Lys8]Vasopressin, the First V1b-Selective Agonist for Rat Vasopressin/Oxytocin Receptors. Endocrinology, 148, 4136-4146. [Google Scholar] [CrossRef] [PubMed]
[63] Corbani, M., Trueba, M., Stoev, S., Murat, B., Mion, J., Boulay, V., et al. (2011) Design, Synthesis, and Pharmacological Characterization of Fluorescent Peptides for Imaging Human V1b Vasopressin or Oxytocin Receptors. Journal of Medicinal Chemistry, 54, 2864-2877. [Google Scholar] [CrossRef] [PubMed]
[64] Gal, C.S., Wagnon, J., Tonnerre, B., Roux, R., Garcia, G., Griebel, G., et al. (2006) An Overview of SSR149415, a Selective Nonpeptide Vasopressin V1b Receptor Antagonist for the Treatment of Stress-Related Disorders. CNS Drug Reviews, 11, 53-68. [Google Scholar] [CrossRef] [PubMed]
[65] Griebel, G., Simiand, J., Serradeil-Le Gal, C., Wagnon, J., Pascal, M., Scatton, B., et al. (2002) Anxiolytic-and Antidepressant-Like Effects of the Non-Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Suggest an Innovative Approach for the Treatment of Stress-Related Disorders. Proceedings of the National Academy of Sciences, 99, 6370-6375. [Google Scholar] [CrossRef] [PubMed]
[66] Iijima, M., Yoshimizu, T., Shimazaki, T., Tokugawa, K., Fukumoto, K., Kurosu, S., et al. (2014) Antidepressant and Anxiolytic Profiles of Newly Synthesized Arginine Vasopressin V1b Receptor Antagonists: TASP0233278 and tasp0390325. British Journal of Pharmacology, 171, 3511-3525. [Google Scholar] [CrossRef] [PubMed]
[67] Robben, J.H., Sze, M., Knoers, N.V., Eggert, P., Deen, P. and Mu[Combining Diaeresis]ller, D. (2007) Relief of Nocturnal Enuresis by Desmopressin Is Kidney and Vasopressin Type 2 Receptor Independent. Journal of the American Society of Nephrology, 18, 1534-1539. [Google Scholar] [CrossRef] [PubMed]
[68] Hines, C.B., Hooper, G.L. and Collins-Yoder, A. (2020) Tolvaptan for Autosomal Dominant Polycystic Kidney Disease: Pharmacokinetics and Implications for Practice. Nephrology Nursing Journal, 47, 145-150. [Google Scholar] [CrossRef] 
[69] Nakamura, S., Hirano, T., Tsujimae, K., Aoyama, M., Kondo, K., Yamamura, Y., et al. (2000) Antidiuretic Effects of a Nonpeptide Vasopressin V2-Receptor Agonist, OPC-51803, Administered Orally to Rats. The Journal of Pharmacology and Experimental Therapeutics, 295, 1005-1011. [Google Scholar] [CrossRef] 
[70] Tanemoto, M. (2023) Vasopressin V2 Receptor Antagonists for the Syndrome of Inappropriate Antidiuretic Hormone Secretion. International Urology and Nephrology, 56, 361-362. [Google Scholar] [CrossRef] [PubMed]
[71] Yamaguchi, K., Shijubo, N., Kodama, T., Mori, K., Sugiura, T., Kuriyama, T., et al. (2010) Clinical Implication of the Antidiuretic Hormone (ADH) Receptor Antagonist Mozavaptan Hydrochloride in Patients with Ectopic ADH Syndrome. Japanese Journal of Clinical Oncology, 41, 148-152. [Google Scholar] [CrossRef] [PubMed]
[72] Wang, X., Constans, M.M., Chebib, F.T., Torres, V.E. and Pellegrini, L. (2019) Effect of a Vasopressin V2 Receptor Antagonist on Polycystic Kidney Disease Development in a Rat Model. American Journal of Nephrology, 49, 487-493. [Google Scholar] [CrossRef] [PubMed]
[73] Fouillen, A., Bous, J., Couvineau, P., Orcel, H., Mary, C., Pierre, T., Mendre, C., Gilles, N., Schulte, G., Granier, S. and Mouillac, B. (2024) Inactive Structures of the Vasopressin V2 Receptor Reveal Distinct Antagonist Binding Modes for Tolvaptan and Mambaq-Uaretin Toxin.
[74] Kee, T.R., Khan, S.A., Neidhart, M.B., Masters, B.M., Zhao, V.K., Kim, Y.K., et al. (2024) The Multifaceted Functions of β-Arrestins and Their Therapeutic Potential in Neurodegenerative Diseases. Experimental & Molecular Medicine, 56, 129-141. [Google Scholar] [CrossRef] [PubMed]
[75] Haider, R.S., Matthees, E.S.F., Drube, J., Reichel, M., Zabel, U., Inoue, A., et al. (2022) β-Arrestin1 and 2 Exhibit Distinct Phosphorylation-Dependent Conformations When Coupling to the Same GPCR in Living Cells. Nature Communications, 13, Article No. 5638. [Google Scholar] [CrossRef] [PubMed]
[76] Carino, C.M.C., Hiratsuka, S., Kise, R., Nakamura, G., Kawakami, K., Yanagawa, M., et al. (2025) Signal Profiles and Spatial Regulation of β-Arrestin Recruitment through Gβ5 and GRK3 at the Μ-Opioid Receptor. European Journal of Pharmacology, 987, Article ID: 177151. [Google Scholar] [CrossRef] [PubMed]

为你推荐