Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands.
J Biol Chem
; 289(39): 27055-27064, 2014 Sep 26.
Article
en En
| MEDLINE
| ID: mdl-25107910
ABSTRACT
Drug-induced taste disturbance is a common adverse drug reaction often triggered by drug secretion into saliva. Very little is known regarding the molecular mechanisms underlying salivary gland transport of xenobiotics, and most drugs are assumed to enter saliva by passive diffusion. In this study, we demonstrate that salivary glands selectively and highly express OCT3 (organic cation transporter-3), a polyspecific drug transporter in the solute carrier 22 family. OCT3 protein is localized at both basolateral (blood-facing) and apical (saliva-facing) membranes of salivary gland acinar cells, suggesting a dual role of this transporter in mediating both epithelial uptake and efflux of organic cations in the secretory cells of salivary glands. Metformin, a widely used anti-diabetic drug known to induce taste disturbance, is transported by OCT3/Oct3 in vitro. In vivo, metformin was actively transported with a high level of accumulation in the salivary glands of wild-type mice. In contrast, active uptake and accumulation of metformin in salivary glands were abolished in Oct3(-/-) mice. Oct3(-/-) mice also showed altered metformin pharmacokinetics and reduced drug exposure in the heart. These results demonstrate that OCT3 is responsible for metformin accumulation and secretion in salivary glands. Our study uncovered a novel carrier-mediated pathway for drug entry into saliva and sheds new light on the molecular mechanisms underlying drug-induced taste disorders.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Glándulas Salivales
/
Factor 3 de Transcripción de Unión a Octámeros
/
Hipoglucemiantes
/
Metformina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2014
Tipo del documento:
Article