The signaling of protease-activated receptor-2 activating peptide-induced contraction in cat esophageal smooth muscle cells
- Authors
- Ha, Hyun Su; Lee, Se Eun; Lee, Hyun Seok; Kim, Gil Hyung; Yoon, Chan Jong; Han, Jong Soo; Lee, Ji-Yun; Sohn, Uy Dong
- Issue Date
- Dec-2017
- Publisher
- PHARMACEUTICAL SOC KOREA
- Keywords
- PAR2-AP; Cat esophageal smooth muscle cells; Contraction; G proteins
- Citation
- ARCHIVES OF PHARMACAL RESEARCH, v.40, no.12, pp 1443 - 1454
- Pages
- 12
- Journal Title
- ARCHIVES OF PHARMACAL RESEARCH
- Volume
- 40
- Number
- 12
- Start Page
- 1443
- End Page
- 1454
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/3554
- DOI
- 10.1007/s12272-017-0975-1
- ISSN
- 0253-6269
1976-3786
- Abstract
- Protease-activated receptors (PARs) are a family of G protein-coupled receptors with a unique activation mechanism involving proteolytic cleavage of the extracellular N-terminal domain of the receptor. PAR2 has a contractile effect on esophageal smooth muscle. We investigate the signaling pathways of the PAR2-activating peptide (PAR2-AP) induced contraction in cat esophageal smooth muscle cells. The length of freshly isolated smooth muscle cells and permeabilized cells from feline esophagus were measured by scanning micrometry, and by confirming molecular basis via western blot analysis. The responses to PAR2-AP were initial and sustained contractions, depending on time. The maximum contraction of the initial phase occurred at 60 s. The PAR2-AP-induced contraction was mediated by G alpha i1, G alpha i3, and G alpha q protein activation, leading to phospholipase-c (PLC) and myosin light chain kinase (MLCK) activation. 20 kDa myosin light chain (MLC20) was phosphorylated by PAR2-AP. Rho kinase-2 (ROCK-2), an activator of 17 kDa C-kinase potentiated Protein phosphatase-1 Inhibitor (CPI-17), was increased by PAR2 receptor activation. In conclusion, PAR2-AP produced an initial contraction mediated by G alpha i1, G alpha i3, and G alpha q protein activation, resulting in PLC and MLCK activation. The sustained contraction by PAR2-AP was mediated by the Rho/Rho kinase-dependent pathway.
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