Localization and Functional Characterization of the Cannabinoid Receptor Type 1 (CB1R) in the Kidney

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Rein, Joshua L., Mackie, Ken, Kleyman, Thomas R., Satlin, Lisa M.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.L7733

Introduction Cannabis and synthetic cannabinoid consumption is increasing worldwide. The impact of their consumption on human health including the risk of kidney disease and its associated complications is uncertain. The kidney, among other organs, produces endogenous cannabinoids (endocannabinoids, ECs) that act on the G‐protein‐coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). ECs and CB1R agonists acutely act as diuretics with variable effects on Na+, K+, and HCO3– excretion. As the aldosterone sensitive distal nephron (ASDN) is responsible for the final renal regulation of total body electrolyte, acid/base, and water balance that is mediated by principal cells (PCs) and intercalated cells (ICs), we sought to examine the cell specific expression of components of the EC system in the mouse collecting duct and the acute changes in urine composition after administration of the cannabinoid receptor agonist WIN55,212‐2 (WIN). Methods CB1R and AQP2 localization were examined by immunofluorescence microscopy in cryosections of kidneys harvested from non‐manipulated male C57BL/6 mice (7‐12 weeks of age) using protein‐specific Abs. A subset of whole animal metabolic studies were performed in mice that were acid‐loaded by provision of 20 mM NH4Cl and 1% sucrose added to the drinking water x 7d. On the day of experimentation, mice were allowed to spontaneously void, then injected SC with either 1.5 mg/kg WIN or vehicle control (10% Tween‐80 and 10% DMSO in 1x PBS) in a volume