Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycogen synthase kinase 3beta (GSK3beta), a serine/threonine protein kinase, is a key target of drug discovery in several diseases, including diabetes and Alzheimer disease. Because lithium, a potent inhibitor of GSK3beta, causes nephrogenic diabetes insipidus, GSK3beta may play a crucial role in regulating water homeostasis. We developed renal collecting duct-specific GSK3beta knockout mice to determine whether deletion of GSK3beta affects arginine vasopressin-dependent renal water reabsorption. Although only mildly polyuric under normal conditions, knockout mice exhibited an impaired urinary concentrating ability in response to water deprivation or treatment with a vasopressin analogue. The knockout mice had reduced levels of mRNA, protein, and membrane localization of the vasopressin-responsive water channel aquaporin 2 compared with wild-type mice. The knockout mice also expressed lower levels of pS256-AQP2, a phosphorylated form crucial for membrane trafficking. Levels of cAMP, a major regulator of aquaporin 2 expression and trafficking, were also lower in the knockout mice. Both GSK3beta gene deletion and pharmacologic inhibition of GSK3beta reduced adenylate cyclase activity. In summary, GSK3beta inactivation or deletion reduces aquaporin 2 expression by modulating adenylate cyclase activity and cAMP generation, thereby impairing responses to vasopressin in the renal collecting duct.
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PMID:GSK3beta mediates renal response to vasopressin by modulating adenylate cyclase activity. 2005 51

The renin-angiotensin system (RAS) has been postulated to regulate not only systemic hemodynamic and hydromineral homeostasis but also individualorgan function in the normal condition. On the other hand, its systemic and localactivationleads to hypertension and diabetes mellitus,resulting intarget end organ damage.RAS in the brain is also well known to be involved in the pathogenesis and progression of neuronal disease, as well as regulating blood pressure, sympathetic activity, vasopressin secretion, thirst and sodium appetite.There is increasing evidence that RAS may contribute to neuroinflammation associated with many neuronal diseases in several animal models. Moreover, recent clinical evidence indicates that RAS blockade, including that byangiotensin converting enzyme inhibitors and angiotensin II receptor blockers, has beneficial effects in treating stroke, cognitive dysfunction, Alzheimer disease and other neuronal diseases, suggesting the potential of RAS as a new therapeutic target in neuronal diseases. This article reviews the recent findings ofbrain RAS involvement and thetherapeutic potential of regulating RAS in neuronal disease.
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PMID:Therapeutic approach for neuronal disease by regulating renin-angiotensin system. 2397 91


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