Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 32
Distinct signaling and actions caused by intracellular ligands (pepducins) for proteinaseactivated
receptor-1 in multiple cells/tissues
Satoko Kubo, Tsuyoshi Ishiki, Ichiko Doe, Fumiko Sekiguchi, Hiroyuki Nishikawa*,
Kenzo Kawai*, Atsufumi Kawabata.
Division of Physiology and Pathophysiology, School of Pharmaceutical Sciences, Kinki
University, Higashi-Osaka 577-8502, Japan and *Fuso Pharmaceutical Industries Ltd.,
Osaka 536-8523, Japan. E-mail: 0544410001t@kindai.ac.jp
Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor for thrombin, can be
activated by an N-palmitoylated peptide based on the intracellular loop 3 of human PAR-1,
Pal-RCLSSSAVANRSKKSRALF-amide (P1pal-19), in a C-terminal-dependent manner in
human platelets or PAR1-transfected cells. In contrast, the shorter peptide, Pal-
RCLSSSAVANRS-amide (P1pal-12), could be a PAR1 antagonist. We thus examined the
actions of those peptides in multiple cells/tissues known to express PAR1. P1pal-19, like the
extracellular PAR1 agonist TFLLR-amide (TF), caused Ca2+ signal in human lung epithelial
cells and rat gastric mucosal epithelial cells, and also delayed prostaglandin E2 formation in
the latter cells. P1pal-19 and TF produced endothelial NO-dependent vasodilation and
epithelial prostanoid-dependent bronchodilation. However, P1pal-19 failed to mimic the
contractile activity of TF in the endothelium-denuded blood vessels and gastric smooth
muscle. In contrast, P1pal-12 partially inhibited vasorelaxation by TF and P1pal-19. In sum,
P1pal-19 mimics the actions of TF in the endothelial and epithelial, but not smooth muscle,
cells/tissues, and P1pal-12 may act as a PAR-1 antagonist in the vascular endothelium.
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