Agonists of Orally Expressed TRP Channels Stimulate Salivary Secretion and Modify the Salivary Proteome.

Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.

Differences in the Natural Enamel Surface and Acquired Enamel Pellicle following Exposure to Citric or Hydrochloric Acid.

OBJECTIVES: The aim of this study was to investigate variations in the interaction between enamel, that is, the acquired enamel pellicle (AEP) and citric or hydrochloric acid. MATERIALS AND METHODS: A 24-h AEP was formed on natural enamel specimens (n = 40) from pooled whole mouth human saliva. Samples were randomly allocated to citric (0.3%, pH 3.2) or hydrochloric (HCl) acid (0.01 M, pH 2.38) exposure for 30 or 300 s. The total protein concentration (TPC), and phosphorous and calcium concentrations of the pellicle were determined before and after acid exposure, and again after re-immersion in saliva. Surface roughness and tandem scanning confocal microscopy imaging were used to assess enamel changes. RESULTS: After 300 s of citric acid exposure, the mean ± SD TPC reduced from 5.1 ± 1.1 to 3.5 ± 1.1 mg/mL (p < 0.05). In contrast, after 300 s of HCl exposure, the mean TPC did not reduce significantly from baseline (6.6 ± 1.1 to 5.7 ± 0.7 mg/mL) but was significantly reduced in the reformed pellicle to 4.9 ± 1.2 mg/mL (p < 0.001). This reduction occurred after significant release of calcium and phosphorous from the enamel surface (p < 0.001). Thirty seconds of exposure to either acid had no obvious effect on the AEP. The surface roughness of the enamel decreased after acid exposure but no differences between groups was observed. CONCLUSIONS: These findings indicate that citric acid interacted with proteins in the AEP upon contact, offering enamel protection. In contrast, HCl appeared to bypass the pellicle, and reduced protein was observed only after changes in the enamel chemical composition.

Sensory effects of transient receptor potential channel agonists on whole mouth saliva extensional rheology.

The extensional rheology (ER) of saliva is a property associated with its ability to coat surfaces and is important for the maintenance of a normal mouth feeling. Transient receptor potential (TRP) channels are expressed in the oral cavity and this study investigated how the sensory effects of TRP channel agonists modify the ER of saliva. Healthy volunteers rinsed with solutions containing a TRP agonist. Unstimulated whole mouth saliva (WMS) was collected prior to rinsing and WMS was collected during the first and second minutes after the mouth rinse. The Spinnbarkeit of the collected saliva was measured using a Neva Meter. The nonivamide (TRPV1) mouth rinse increased WMS ER from 37.0 (± 6.3) mm to 49.3 (± 5.1) mm when compared with the vehicle control, which itself had no effect on WMS ER. However, this effect was short-lived and ER of WMS was not increased in the second minute after the nonivamide mouth rinse. The menthol (TRPM8) mouth rinse resulted in an increase up to 57.8 (± 7.8) mm in WMS ER from the vehicle control and returned to control levels in the second minute. The cinnamaldehyde (TRPA1) mouth rinse resulted in no change in WMS ER. It can be concluded that nonivamide and menthol mouth rinsing has a short-term effect of increasing WMS ER, an effect not observed after cinnamaldehyde rinsing. We hypothesize that the activation of some TRP channels in the oral cavity results in changes in the salivary protein composition that in turn alters WMS ER. PRACTICAL APPLICATIONS: Identifying compounds that modify the physical properties of saliva in a desirable way is important in developing treatments for conditions associated with changes in the physical properties of saliva such as xerostomia (also known as dry mouth). Furthermore, understanding the rheology of saliva contributes to the elucidation of food oral processing which is of importance to food manufacturers.