[Roles of protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, in modulation of exocrine gland functions].
Protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, is activated by proteolytic unmasking of the N-terminal extracellular tethered ligand that presumably binds to the extracellular loop 2 of the receptor itself. PAR-2 is widely distributed in the mammalian body and plays various roles in biological events in the cardiovascular, respiratory, alimentary, and central neurons systems. PAR-2-activating peptides administered systemically to mice and rats trigger prompt salivation in vivo. In an in vitro study, PAR-2 agonists including the endogenous PAR-2 activator trypsin induce secretion of amylase and mucin from isolated rat parotid glands and sublingual glands, respectively. PAR-2-activating peptides administered systemically also modulate pancreatic exocrine secretion in vivo as well as in vitro. In the gastric mucosa, PAR-2 stimulation enhances secretion of mucus and pepsinogen and suppresses acid secretion. Tear secretion can also be caused by PAR-2-related peptides in PAR-2-dependent and -independent manners. PAR-2 thus plays a general or key role in the regulation of exocrine secretion. This review focuses on the physiologic and/or pathophysiologic roles of PAR-2 in glandular exocrine secretion. The possibility of PAR-2 as a target for drug development is also discussed.
Nishikawa
Hiroyuki
H
Research and Development Center, Fuso Pharmaceutical Industries, Ltd., Morinomiya, Osaka, Japan. h-nishikawa@fuso-pharm.co.jp
D000818:Animals; D015195:Drug Design; D005088:Exocrine Glands / Q000378:metabolism*; D005750:Gastric Juice / Q000378:metabolism; D051379:Mice; D010189:Pancreatic Juice / Q000378:metabolism; D051381:Rats; D044464:Receptor, PAR-2 / Q000502:physiology*; D012463:Saliva / Q000378:metabolism; D013666:Tears / Q000378:metabolism
D044464:Receptor, PAR-2