TRPV6 channel mediates alcohol-induced gut barrier dysfunction and systemic response
Avtar S. Meena, Pradeep K. Shukla, Briar Bell, Francesco Giorgianni, Rebeca Caires, Carlos Fernández‐Peña, Sarka Beranova, Eitaro Aihara, Marshall H. Montrose, Mehdi Chaib, Liza Makowski, Indira Neeli, Marko Radic, Valeria Vásquez, Jonathan H. Jaggar, Julio F. Cordero-Morales, Radhakrishna Rao
Abstract
mice are resistant to alcohol-induced intestinal barrier dysfunction. Photoaffinity labeling of 3-azibutanol identifies a histidine as a potential alcohol-binding site in TRPV6. The substitution of this histidine, and a nearby arginine, reduces ethanol-activated currents. Our findings reveal that TRPV6 is required for alcohol-induced gut barrier dysfunction and inflammation. Molecules that decrease TRPV6 function have the potential to attenuate alcohol-associated tissue injury.