The zinc receptor, ZnR/GPR39, modulates taste sensitivity by regulating ion secretion in mouse salivary gland

Reduced saliva secretion, dry mouth, and loss of taste are debilitating symptoms associated with zinc deficiency. A mechanism for zinc regulation of these processes is lacking. Here, we identified the Zn²⁺ sensing receptor ZnR/GPR39 as a mediator of ion transport in salivary gland epithelium. By monitoring transport of NH₄⁺, a surrogate for K⁺, we revealed that Zn²⁺ upregulates the Na⁺/K⁺ ATPase pump activity in parotid and submandibular salivary gland epithelium from wildtype (WT), but not from ZnR/GPR39 knockout (KO), mice. Since Na⁺/K⁺ ATPase activity is crucial for solute transport, we compared saliva composition in WT and ZnR/GPR39 KO mice and found impaired ionic concentration and reduced saliva secretion in ZnR/GPR39 KO mice. Moreover, mice deficient in ZnR/GPR39 exhibited decreased sensitivity to appetitive Na⁺ concentrations. Altogether, we demonstrate that salivary ZnR/GPR39 activity controls saliva ion composition and secretion, and provides a target for therapeutic approaches for dry mouth and taste disorders.