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.