Protease-activated receptor-2 (PAR-2) in the pancreas and parotid gland: Immunolocalization and involvement of nitric oxide in the evoked amylase secretion.
Protease-activated receptor-2, a G protein-coupled receptor activated by serine proteases such as trypsin, tryptase and coagulation factors VIIa and Xa, modulates pancreatic and salivary exocrine secretion. In the present study, we examined the distribution of PAR-2 in the pancreas and parotid gland, and characterized the PAR-2-mediated secretion of amylase by these tissues in vivo. Immunohistochemical analyses using the polyclonal antibody against rat PAR-2 clearly showed abundant expression of PAR-2 in rat pancreatic and parotid acini. The PAR-2 agonist SLIGRL-NH2, administered intraperitoneally (i.p.) at 1-10 micromol/kg and 1.5-15 micromol/kg, in combination with amastatin, an aminopeptidase inhibitor, facilitated in vivo secretion of pancreatic and salivary amylase in a dose-dependent manner, respectively, in the mouse. The PAR-2-mediated secretion of pancreatic amylase was abolished by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor. The secretion of salivary amylase in response to the PAR-2 agonist at a large dose, 15 micromol/kg, but not at a smaller dose, 5 micromol/kg, was partially reduced by L-NAME. Pretreatment with capsaicin for ablation of the sensory neurons did not modify the PAR-2-mediated secretion of pancreatic and salivary amylase in the mouse. In conclusion, our study demonstrates expression of PAR-2 in rat pancreatic acini as well as parotid acini and indicates that nitric oxide participates in the PAR-2-mediated in vivo secretion of pancreatic amylase, and, to a certain extent, of salivary amylase, although capsaicin-sensitive sensory neurons, known to be activated by PAR-2, are not involved in the evoked pancreatic or salivary amylase secretion.
Kawabata
Atsufumi
A
Department of Pathophysiology & Therapeutics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, 577-8502, Higashi-Osaka, Japan. kawabata@phar.kindai.ac.jp
Kuroda
Ryotaro
R
Nishida
Minoru
M
Nagata
Nanae
N
Sakaguchi
Yuriko
Y
Kawao
Naoyuki
N
Nishikawa
Hiroyuki
H
Arizono
Naoki
N
Kawai
Kenzo
K
D000595:Amino Acid Sequence; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010179:Pancreas / Q000378:metabolism*; D010306:Parotid Gland / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000737:chemistry / Q000378:metabolism*
D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000681:Amylases; D019331:NG-Nitroarginine Methyl Ester