水通道蛋白2
内分泌学
内科学
大麻素
内大麻素系统
肾
加压素
受体
化学
大麻素受体
利尿
肾源性尿崩症
塔姆-霍斯法尔蛋白
尿崩症
多尿
兴奋剂
医学
糖尿病
机械工程
水道
工程类
入口
作者
Joshua L. Rein,Ken Mackie,Thomas R. Kleyman,Lisa M. Satlin
出处
期刊:American Journal of Physiology-renal Physiology
[American Physiological Society]
日期:2024-04-18
标识
DOI:10.1152/ajprenal.00320.2022
摘要
Cannabis and synthetic cannabinoid consumption is increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G-protein-coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids (ECs), endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total-body water and electrolyte homeostasis. As the kidney collecting duct (CD) regulates total body water, acid/base, and electrolyte balance through specific functions of principal cells (PCs) and intercalated cells (ICs), we examined the cell-specific immunolocalization of CB1R in the mouse CD. Antibodies against either the C-terminus or N-terminus of CB1R consistently labeled AQP2(-) cells in the cortical and medullary CD, and thus presumably ICs. Given the well-established role of ICs in urinary acidification, we utilized a clearance approach in mice that were acid-loaded with 280 mM NH4Cl for 7d and non-acid-loaded mice treated with the cannabinoid receptor agonist, WIN55,212-2 (WIN), or a vehicle control. While WIN had no effect on urinary acidification, these WIN-treated mice had less apical+subapical AQP2 expression in PCs compared to controls and developed an acute diabetes insipidus (DI) associated with the excretion of large volumes of dilute urine. Mice maximally concentrated their urine when WIN + 1-desamino-8-d-arginine-vasopressin (desmopressin, DDAVP) were co-administered, consistent with central rather than nephrogenic DI. Although ICs express CB1R, the physiologic role of CB1R in this cell type remains to be determined.
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