Lipopolysaccharide-induced subsensitivity of protease-activated receptor-2 in the mouse salivary glands in vivo.
Protease-activated receptor-2 (PAR-2) acts as a modulator of multiple physiological/pathophysiological functions including salivary exocrine secretion. Given the supersensitivity of endothelial PAR-2 under endotoxaemia, we investigated if endotoxin/lipopolysaccharide (LPS) could alter the sensitivity of PAR-2 in the salivary glands. The in vivo salivation in response to i.v. administration of the PAR-2-activating peptide SLIGRL-NH2, but not of carbachol, gradually decreased 6-20 h after LPS administration in the mice. The LPS-induced hyporeactivity to the PAR-2 agonist was partially reversed by repeated administration of aprotinin, a non-specific protease inhibitor. PAR-2 mRNA levels in the salivary glands, as assessed by the semi-quantitative RT-PCR analysis, remained unchanged following LPS challenge. Our findings indicate that in contrast to the supersensitivity of endothelial PAR-2 as described previously, subsensitivity of PAR-2 in the salivary glands develops during the LPS-induced systemic inflammation, which might involve desensitisation of PAR-2 by endogenous proteases.
Kawabata
A
A
Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
Kuroda
R
R
Morimoto
N
N
Kawao
N
N
Masuko
T
T
Kakehi
K
K
Kataoka
K
K
Taneda
M
M
Nishikawa
H
H
Araki
H
H
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D007611:Aprotinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004347:Drug Interactions; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism; D012472:Salivation / Q000187:drug effects
D000998:Antiviral Agents; D008070:Lipopolysaccharides; D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D002217:Carbachol; D007611:Aprotinin