Proteomics

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Agonists of orally expressed TRP channels stimulate salivary secretion and modify the salivary proteome


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 to 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 mass spectrometry 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 non-salivary 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

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Saliva

SUBMITTER: Jack Houghton  

LAB HEAD: Gordon Proctor

PROVIDER: PXD017232 | Pride | 2020-07-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
PR484_JH_TMT1_1_7.raw Raw
PR484_JH_TMT1_1_7_6_12_IEF_Mudpit_HT.msf Msf
PR484_JH_TMT1_1_7_6_12_IEF_Mudpit_HT.xlsx Xlsx
PR484_JH_TMT1_1_7_6_12_IEF_Mudpit_HT_protein.xlsx Xlsx
PR484_JH_TMT1_2_8.raw Raw
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Publications

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

Houghton Jack William JW   Carpenter Guy G   Hans Joachim J   Pesaro Manuel M   Lynham Steven S   Proctor Gordon G  

Molecular & cellular proteomics : MCP 20200710 10


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  ...[more]

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