Mechanism of diuresis and natriuresis by cannabinoids: Evidence for inhibition of_ na+-K+-ATPase in mouse kidney thick ascending limb tubules

Joseph K. Ritter, Ashfaq Ahmad, Shobha Mummalaneni, Zdravka Daneva, Sara K. Dempsey, Ningjun Li, Pin Lan Li, Vijay Lyall

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The endocannabinoid, anandamide (AEA), stimulates cannabinoid receptors (CBRs) and is enriched in the kidney, especially the renal medulla. AEA infused into the renal outer medulla of mice stimulates urine flow rate and salt excretion. Here we show that these effects are blocked by the CBR type 1 (CB1) inverse agonist, rimonabant. Immunohistochemical analysis demonstrated the presence of CB1 in thick ascending limb (TAL) tubules. Western immunoblotting demonstrated the presence of CB1 (52 kDa) in the cortex and outer medulla of mouse kidney. The effect of direct [CP55940 (CP) or AEA] or indirect [fatty acyl amide hydrolase (FAAH) inhibitor, PF3845 (PF)] cannabinoidimetics on Na+ transport in isolated mouse TAL tubules was studied using the Na+-sensitive dye, SBFI-AM. Switching from 0 Na+ solution to control Ringer’s solution (CR) rapidly increased TAL cell [Na+]i. Addition of CP to CR produced a further elevation, similar in magnitude to that of ouabain, a Na+-K+-ATPase inhibitor. This [Na+]i-elevating effect of CP was time-dependent, required the presence of Na+ in the bathing solution, and was insensitive to Na+-K+-2Cl2 cotransporter inhibition. Addition of PF to CR elevated [Na+]i in FAAH wild-type but not FAAH knockout (KO) TALs, whereas the additions of CP and AEA to PF-treated FAAH KO TALs increased [Na+]i. An interaction between cannabinoidimetics and ouabain (Ou) was observed. Ou produced less increase in [Na+]i after cannabinoidimetic treatment, whereas cannabinoidimetics had less effect after Ou treatment. It is concluded that cannabinoidimetics, including CP and AEA, inhibit Na+ transport in TALs by inhibiting Na+ exit via Na+-K+-ATPase.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume376
Issue number1
DOIs
StatePublished - Jan 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint

Dive into the research topics of 'Mechanism of diuresis and natriuresis by cannabinoids: Evidence for inhibition of_ na+-K+-ATPase in mouse kidney thick ascending limb tubules'. Together they form a unique fingerprint.

Cite this