Targeting the Trafficking of Kidney Water Channels for Therapeutic Benefit

被引:30
|
作者
Cheung, Pui W.
Bouley, Richard
Brown, Dennis [1 ]
机构
[1] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA
来源
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 60 | 2020年 / 60卷
基金
美国国家卫生研究院;
关键词
aquaporin-2; urine concentration; vasopressin receptor type 2; collecting duct principal cells; endocytosis; exocytosis; NEPHROGENIC DIABETES-INSIPIDUS; RENAL COLLECTING DUCT; EPIDERMAL-GROWTH-FACTOR; ADENYLATE-CYCLASE; ANGIOTENSIN-II; AQUAPORIN; IN-VIVO; RAT-KIDNEY; PHOSPHODIESTERASE INHIBITOR; URINARY CONCENTRATION;
D O I
10.1146/annurev-pharmtox-010919-023654
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The ability to regulate water movement is vital for the survival of cells and organisms. In addition to passively crossing lipid bilayers by diffusion, water transport is also driven across cell membranes by osmotic gradients through aquaporin water channels. There are 13 aquaporins in human tissues, and of these, aquaporin-2 (AQP2) is the most highly regulated water channel in the kidney: The expression and trafficking of AQP2 respond to body volume status and plasma osmolality via the antidiuretic hormone, vasopressin (VP). Dysfunctional VP signaling in renal epithelial cells contributes to disorders of water balance, and research initially focused on regulating the major cAMP/PKA pathway to normalize urine concentrating ability. With the discovery of novel and more complex signaling networks that regulate AQP2 trafficking, promising therapeutic targets have since been identified. Several strategies based on data from preclinical studies may ultimately translate to the care of patients with defective water homeostasis.
引用
收藏
页码:175 / 194
页数:20
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