TY - JOUR
T1 - Involvement of Gi/o in the PAR-4-induced NO production in endothelial cells
AU - Momota, Fumi
AU - Hirano, Katsuya
AU - Hirano, Mayumi
AU - Nishimura, Junji
AU - Kanaide, Hideo
N1 - Funding Information:
We thank Mr. Brian Quinn for linguistic comments and help with the manuscript. This study was supported in part by the grant from the 21st Century COE Program, Grants-in-Aid for Scientific Research (Nos. 16590695, 17590222, 17590744, and 17790493) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Mochida Memorial Foundation for Medical and Pharmaceutical Research.
PY - 2006/4/7
Y1 - 2006/4/7
N2 - We investigated the involvement of Gi/o protein in NO production following the activation of proteinase-activated receptor-4 (PAR-4) in cultured bovine aortic endothelial cells. AYPGKF-NH2 (PAR-4 activating peptide), thrombin, and ionomycin induced a concentration-dependent NO production, with the maximal production seen at 30 μM, 0.1 U/ml, and 1 μM, respectively. Ionomycin elevated [Ca2+]i in a concentration-dependent manner. However, AYPGKF-NH2 and thrombin induced no [Ca2+]i elevation. The loading of cells with BAPTA almost completely inhibited both the NO production and [Ca 2+]i elevation induced by 1 μM ionomycin, while it had no significant effect on the AYPGKF-NH2-induced NO production. Treatment with pertussis toxin inhibited the AYPGKF-NH2-induced NO production, while it had no effect on the ionomycin-induced NO production. Our findings thus demonstrate, for the first time, that PAR-4 activation induced NO production in a manner mostly independent of the Ca2+ signal and also that Gi/o is involved in such NO production in vascular endothelial cells.
AB - We investigated the involvement of Gi/o protein in NO production following the activation of proteinase-activated receptor-4 (PAR-4) in cultured bovine aortic endothelial cells. AYPGKF-NH2 (PAR-4 activating peptide), thrombin, and ionomycin induced a concentration-dependent NO production, with the maximal production seen at 30 μM, 0.1 U/ml, and 1 μM, respectively. Ionomycin elevated [Ca2+]i in a concentration-dependent manner. However, AYPGKF-NH2 and thrombin induced no [Ca2+]i elevation. The loading of cells with BAPTA almost completely inhibited both the NO production and [Ca 2+]i elevation induced by 1 μM ionomycin, while it had no significant effect on the AYPGKF-NH2-induced NO production. Treatment with pertussis toxin inhibited the AYPGKF-NH2-induced NO production, while it had no effect on the ionomycin-induced NO production. Our findings thus demonstrate, for the first time, that PAR-4 activation induced NO production in a manner mostly independent of the Ca2+ signal and also that Gi/o is involved in such NO production in vascular endothelial cells.
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U2 - 10.1016/j.bbrc.2006.01.165
DO - 10.1016/j.bbrc.2006.01.165
M3 - Article
C2 - 16483540
AN - SCOPUS:33344472078
VL - 342
SP - 365
EP - 371
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -