Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.6.1.2 (
guanylate cyclase
)
8,497
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to the antidiuretic hormone arginine vasopressin (AVP), which leads to polyuria, plasma hyperosmolarity, polydipsia, and impaired quality of living. Inherited forms are caused by X-linked loss-of-function mutations in the gene encoding the vasopressin 2 receptor (V2R) or autosomal recessive/dominant mutations in the gene encoding
aquaporin 2
(
AQP2
). A common acquired form is lithium-induced NDI. AVP facilitates reabsorption of water through increased abundance and insertion of
AQP2
in the apical membrane of principal cells in the collecting ducts. In X-linked NDI, V2R is dysfunctional, which leads to impaired water reabsorption. These patients have functional
AQP2
, and thus the challenge is to achieve
AQP2
membrane insertion independently of V2R. The current treatment is symptomatic and is based on distally acting diuretics (thiazide or amiloride) and cyclooxygenase inhibitors (indomethacin). This mini-review covers published data from trials in preclinical in vivo models and a few human intervention studies to improve NDI by more causal approaches. Promising effects on NDI in preclinical studies have been demonstrated by the use of pharmacological approaches with secretin, Wnt5a, protein kinase A agonist, fluconazole, prostaglandin E
2
EP2 and EP4 agonists, statins, metformin, and soluble prorenin receptor agonists. In patients, only casuistic reports have evaluated the effect of statins, phosphodiesterase inhibitors (rolipram and sildenafil), and the
guanylate cyclase
stimulator riociguat without amelioration of symptoms. It is concluded that there is currently no established intervention that causally improves symptoms or quality of life in patients with NDI. There is a need to collaborate to improve study quality and conduct formal trials.
...
PMID:A mini-review of pharmacological strategies used to ameliorate polyuria associated with X-linked nephrogenic diabetes insipidus. 3292 47
