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.

Taste and smell perceptions diminish in older age, impacting upon quality of life and nutrition, yet the causes of taste loss are largely unknown. Transient receptor potential channels (TRP) found on the oral mucosa are also involved in oral sensations including cooling and burning and may contribute to the eating experience of older people. Older adults often have reduced salivary flow and the physical properties of saliva may change, but the role of saliva in oral sensations of older adults is yet to be elucidated. Here, the effect of older age on subjective (perception) and objective (stimulated salivary response) measures of TRP stimulants, odors, and basic tastants was investigated. Whole mouth saliva was collected from younger (mean age 24 years) and older adults (mean age 72 years) following stimulation of taste [mono sodium glutamate (MSG) and caffeine], olfaction (menthol), and TRP receptors (capsaicin). Participants rated perceived intensity of each stimulus, and salivary properties were assessed. Older age was associated with 15% lower umami taste and 26% lower menthol odor perception, coupled with 17% lower salivary response to MSG. Interestingly, there were no differences for perception of TRP stimulants, so chemo-sensation was not affected by age. Younger adults had four times greater elasticity (Spinnbarkeit) with MUC7 levels almost double and 66% greater resting salivary flow rate. Stimulated salivary responses in the younger group were also higher compared to the older group, with changes in protein and viscoelasticity in response to taste and TRP stimulation. These results show the impact of older age upon taste and smell sensation which may lead to changes in the physical and compositional properties of saliva in response to taste/odor stimulation. Measurement of stimulated salivary flow and rheology provides an objective measure of taste in addition to subjective perceptions which can be influenced by participant bias. Chemo-sensation may be retained with age and trigeminal stimuli such as chili could be employed in future studies to enhance meals for an age group at risk of malnutrition. Alteration in salivary properties due to advanced age could impact on ability to taste due to poor diffusion of tastants and reduced oral surface protection.