Abstract
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.
Highlights
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
1 ppm nonivamide and 500 ppm menthol mouth rinsing significantly increased relative mean whole mouth saliva (WMS) flow rates compared with propylene glycol (PG) mouth rinsing, which itself significantly increased WMS flow rates compared with unstimulated WMS (UWMS)
These observations expand on the current reports in the literature that TRPV1 agonists, such as piperine, nonivamide, capsaicin and 6-gingerol can stimulate salivary secretion because stimulation of salivary secretion by menthol has not previously been described
Summary
Highlights Salivary secretion was increased by mouth rinsing with TRP channel agonists. 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. Increased salivary flow rate and specific protein secretion have been demonstrated in response to other tastants [21,22,23,24] and there are studies demonstrating increases in salivary flow rates and specific protein changes in response to the TRPV1 agonists [25,26,27,28,29] but there has been limited study of agonists to other TRP channels, despite expression of these channels in the oral cavity, nor has the mechanism of TRP channel agonist stimulated salivary secretion been elucidated. Studies were conducted to confirm the specific protein changes of the proteomes of salivas identified in the proteomics study and to consider the mechanism by which the compounds exert their effects on the salivary proteomes
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