Physiology and pathophysiology of proteinase-activated receptors (PARs): PARs in the respiratory system: cellular signaling and physiological/pathological roles.
Proteinase-activated receptors (PARs), a family of G protein-coupled receptors, are widely distributed in the mammalian body, playing a variety of physiological/pathophysiological roles. In the respiratory systems, PARs, particularly PAR-2 and PAR-1, are expressed in the epithelial and smooth muscle cells. In addition to the G(q/11)-mediated activation of the phospholipase C beta pathway, epithelial PAR activation causes prompt and/or delayed prostanoid formation, leading to airway smooth muscle relaxation and/or modulation of an inflammatory process. PAR-2 present in the epithelium and smooth muscle is considered primarily pro-inflammatory in the respiratory system, although PAR-2 may also be anti-inflammatory under certain conditions. In the lung epithelial cells, PAR-2 can also be activated by exogenous proteinases including house dust mite allergens, in addition to various possible endogenous agonist proteinases. Clinical evidence also suggests possible involvement of PARs, particularly PAR-2, in respiratory diseases. PARs thus appear to play critical roles in the respiratory systems, and the agonists/antagonists for PARs may serve as the novel therapeutic strategy for treatment of certain respiratory diseases including asthma.
Kawabata
Atsufumi
A
Division of Physiology and Pathophysiology, School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan. kawabata@phar.kindai.ac.jp
Kawao
Naoyuki
N
D000818:Animals; D006801:Humans; D008954:Models, Biological; D044462:Receptors, Proteinase-Activated / Q000145:classification / Q000502:physiology*; D012137:Respiratory System / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*
D044462:Receptors, Proteinase-Activated