Lipopolysaccharide-induced subsensitivity of protease-activated receptor-2in the mouse salivary glands in vivo

Protease-activated receptor-2 (PAR-2) acts as a modulator of multiple physi ological/pathophysiologicaI functions including salivary exocrine secretion . Given the supersensitivity of endothelial PAR-2 under endotoxaemia, we in vestigated if endotoxin/lipopolysaccharide (LPS) could alter the sensitivit y of PAR-2 in the salivary glands. The in vivo salivation in response to i.v. administration of the PAR-2-acti vating peptide SLIGRL-NH2, but not of carbachol, gradually decreased 6-20 h after LPS administration in the mice. The LPS-induced hyporeactivity to th e PAR-2 agonist was partially reversed by repeated administration of aproti nin, a non-specific protease inhibitor. PAR-2 mRNA levels in the salivary g lands, as assessed by the semi-quantitative RT-PCR analysis, remained uncha nged following LPS challenge. Our findings indicate that in contrast to the supersensitivity of endotheli al PAR-2 as described previously, subsensitivity of PAR-2 in the salivary g lands develops during the LPS-induced systemic inflammation, which might in volve desensitisation of PAR-2 by endogenous proteases.