Expression profile of the zinc transporter ZnT3 in taste cells of rat circumvallate papillae and its role in zinc release, a potential mechanism for taste stimulation.

Zinc is an essential trace element, and its deficiency causes taste dysfunction. Zinc accumulates in zinc transporter (ZnT)3-expressing presynaptic vesicles in hippocampal neurons and acts as a neurotransmitter in the central nervous system. However, the distribution of zinc and its role as a signal transmitter in taste buds remain unknown. Therefore, we examined the distribution of zinc and expression profiles of ZnT3 in taste cells and evaluated zinc release from isolated taste cells upon taste stimuli. Taste cells with a spindle or pyriform morphology were revealed by staining with the fluorescent zinc dye ZnAF-2DA and autometallography in the taste buds of rat circumvallate papillae. Znt3 mRNA levels were detected in isolated taste buds. ZnT3-immunoreactivity was found in phospholipase-ß2-immunopositive type II taste cells and aromatic amino acid decarboxylase-immunopositive type III cells but not in nucleoside triphosphate diphosphohydrolase 2-immunopositive type I cells. Moreover, we examined zinc release from taste cells using human transient receptor potential A1-overexpressing HEK293 as zinc-sensor cells. These cells exhibited a clear response to isolated taste cells exposed to taste stimuli. However, pretreatment with magnesium-ethylenediaminetetraacetic acid, an extracellular zinc chelator - but not with zinc-ethylenediaminetetraacetic acid, used as a negative control - significantly decreased the response ratio of zinc-sensor cells. These findings suggest that taste cells release zinc to the intercellular area in response to taste stimuli and that zinc may affect signaling within taste buds.

Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats.

As one of the adverse effects of oxaliplatin, a key agent in colon cancer chemotherapy, a taste disorder is a severe issue in a clinical situation because it decreases the quality of life of patients. However, there is little information on the mechanism underlying the oxaliplatin-induced taste disorder. Here, we examined the molecular and behavioral characteristics of the oxaliplatin-induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and protein of taste receptors in circumvallate papillae (CP) were measured by real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry, respectively. Taste sensitivity was assessed by their behavioral change using a brief-access test. Morphological change of the taste buds in CP was evaluated by hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was counted by immunohistochemical analysis. Among taste receptors, the expression levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief-access test, the lick ratio was decreased in oxaliplatin-administered rats on day 7 and the alteration was recovered to the control level on day 14. There was no detectable alteration in the morphology of taste buds, number of taste cells or plasma zinc level in oxaliplatin-administered rats. These results suggest that decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at least in part, to increased expression of T1R2, while these alterations are reversible.