Capsaicin (trans-8-methyl-N-vanilyl-6-nonenamide) is a unique alkaloid isolated from hot chili peppers of the capsicum family. Capsaicin is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), which is expressed in nociceptive sensory neurons and a range of secretory epithelia, including salivary glands. Capsaicin has analgesic and anti-inflammatory properties in sensory neurons. Recently, increasing evidence has indicated that capsaicin also affects saliva secretion and inflammation in salivary glands. Applying capsaicin increases salivary secretion in human and animal models. Capsaicin appears to increase salivation mainly by modulating the paracellular pathway in salivary glands. Capsaicin activates TRPV1, which modulates the permeability of tight junctions (TJ) by regulating the expression and function of putative intercellular adhesion molecules in an ERK (extracelluar signal-regulated kinase) -dependent manner. Capsaicin also improved dysfunction in transplanted salivary glands. Aside from the secretory effects of capsaicin, it has anti-inflammatory effects in salivary glands. The anti-inflammatory effect of capsaicin is, however, not mediated by TRPV1, but by inhibition of the NF-κB pathway. In conclusion, capsaicin might be a potential drug for alleviating dry mouth symptoms and inflammation of salivary glands.
Sodium bicarbonate cotransporters (NBCs) are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1) and electrogenic NBC (NBCe1), with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs) and HSG cells. Intracellular pH (pHi) was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.
This work was supported by the Korea Science & Engineering Foundation (KOSEF) grant funded by Korea government(R13-2008-008-01001-0) through the Oromaxillofacial Dysfunction Research Center for the Elderly at Seoul National University.
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