Δ9-tetrahydrocannabivarin impairs epithelial calcium transport through inhibition of TRPV5 and TRPV6

Pharmacol Res. 2018 Oct:136:83-89. doi: 10.1016/j.phrs.2018.08.021. Epub 2018 Aug 28.

Abstract

Compounds extracted from the cannabis plant, including the psychoactive Δ9-tetrahydrocannabinol (THC) and related phytocannabinoids, evoke multiple diverse biological actions as ligands of the G protein-coupled cannabinoid receptors CB1 and CB2. In addition, there is increasing evidence that phytocannabinoids also have non-CB targets, including several ion channels of the transient receptor potential superfamily. We investigated the effects of six non-THC phytocannabinoids on the epithelial calcium channels TRPV5 and TRPV6, and found that one of them, Δ9-tetrahydrocannabivarin (THCV), exerted a strong and concentration-dependent inhibitory effect on mammalian TRPV5 and TRPV6 and on the single zebrafish orthologue drTRPV5/6. Moreover, THCV attenuated the drTRPV5/6-dependent ossification in zebrafish embryos in vivo. Oppositely, 11-hydroxy-THCV (THCV-OH), a product of THCV metabolism in mammals, stimulated drTRPV5/6-mediated Ca2+ uptake and ossification. These results identify the epithelial calcium channels TRPV5 and TRPV6 as novel targets of phytocannabinoids, and suggest that THCV-containing products may modulate TRPV5- and TRPV6-dependent epithelial calcium transport.

Keywords: Epithelial calcium transport; Ossification; Phytocannabinoids; TRPV5; TRPV6; Δ(9)-tetrahydrocannabivarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology*
  • Cannabinoids / pharmacology*
  • Embryo, Nonmammalian
  • Epithelium / physiology
  • HEK293 Cells
  • Humans
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / physiology
  • Zebrafish

Substances

  • Cannabinoids
  • TRPV Cation Channels
  • Calcium