Tetrahydrobiopterin (an Activator of NOS) Biosynthesis in the Tongue

Objectives: The taste signal transduction system is an important function in the oral cavity. It is also suggested that taste receptor-cGMP-cyclic nucleotide-gated (CNG) channel is one of the taste signal transduction systems in taste bud cells. Although it was previously reported that tetrahydrobiopterin (BH₄) was contained in saliva, the function of BH₄ in the oral cavity has not been understood yet. BH₄ affects the generation of nitric oxide (NO)-cGMP through the activation of NO synthase (NOS). Therefore, we expected that BH₄ played an important role in the taste signal transduction system through NO-cGMP-CNG channel. In this study, we examined whether the BH₄ biosynthesizing pathway was involved in the tongue. Methods: We prepared paraffin sections of the rat tongue, and then examined the BH₄ biosynthesis by in situ hybridization. We also prepared cryosections of the circumvallate papilla of the rat tongue, and then examined the expression of sepiapterin reductase (SPR), the terminal enzyme of BH₄ biosynthesis using the immunostaining technique. Moreover, we examined the expression of CNG channel in the same manner. Results: Hybridization signals for all enzymes (GTPCH, PTPS, and SPR) of BH₄ biosynthesizing pathway were respectively detected in the rat tongue. We also observed the expression of SPR and CNG channel in taste buds of the circumvallate papilla of the rat tongue. Conclusion: These results suggest that BH₄ is biosynthesized in taste bud cells, and possibly involved in the taste signal transduction system through the NO-cGMP-CNG channel pathway.