Differential Ca2+ responses induced by thrombin and thrombin-receptor agonist peptides in HSY-EA1 cells

被引：4

作者：

Tanimura, A ^{[1
]}

Shitara, A ^{[1
]}

Nezu, A ^{[1
]}

Morita, T ^{[1
]}

Tojyo, Y ^{[1
]}

机构：

[1] Hlth Sci Univ Hokkaido, Sch Dent, Dept Dent Pharmacol, Ishikari, Hokkaido 0610293, Japan

来源：

CELL BIOLOGY INTERNATIONAL | 2003年 / 27卷 / 12期

关键词：

protease-activated receptor; thrombin; calcium; desensitization; SFLLRN; TFLLR;

D O I：

10.1016/j.cellbi.2003.10.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We examined the mechanism by which protease-activated receptor (PAR)-1 is desensitized by comparing the effect of thrombin and the soluble agonist peptide SFLLRN on Ca2+ responses in HSY-EA1 cells. Thrombin-induced increases in cytosolic Ca2+ concentrations ([Ca2+](i)) returned to basal levels within 60 s, but SFLLRN generated a sustained [Ca2+](i) elevation. Interestingly, thrombin-desensitized cells partially retained their ability to respond to SFLLRN. We desensitized PAR-2 by pretreating cells with SLIGKV to confirm that this response was not due to PAR-2, which can recognize SFLLRN. The highly specific PAR-1 agonist peptide TFLLR also increased [Ca2+](i) in PAR-2-desensitized cells pretreated with thrombin. These observations indicate that thrombin disarms PAR-I from further proteolytic activation, but leaves the receptor responsive for non-tethered ligands. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：1017 / 1023

页数：7

共 23 条

[1]

Bohm SK, 1997, BIOCHEM J, V322, P1

[2]

BRASS LF, 1992, J BIOL CHEM, V267, P6044

[3]

BRASS LF, 1994, J BIOL CHEM, V269, P2943

[4]

CHEN J, 1994, J BIOL CHEM, V269, P16041

[5] Functional expression of a human thrombin receptor in Sf9 insect cells: Evidence for an active tethered ligand [J].

Chen, XL ;

Earley, K ;

Luo, WP ;

Lin, SH ;

Schilling, WP .

BIOCHEMICAL JOURNAL, 1996, 314 :603-611

[6] THROMBIN RECEPTOR ACTIVATING PEPTIDES - IMPORTANCE OF THE N-TERMINAL SERINE AND ITS IONIZATION STATE AS JUDGED BY PH-DEPENDENCE, NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY, AND CLEAVAGE BY AMINOPEPTIDASE-M [J].

COLLER, BS ;

WARD, P ;

CERUSO, M ;

SCUDDER, LE ;

SPRINGER, K ;

KUTOK, J ;

PRESTWICH, GD .

BIOCHEMISTRY, 1992, 31 (47) :11713-11720

[7]

GRYNKIEWICZ G, 1985, J BIOL CHEM, V260, P3440

[8] Shutoff and agonist-triggered internalization of protease-activated receptor 1 can be separated by mutation of putative phosphorylation sites in the cytoplasmic tail [J].

Hammes, SR ;

Shapiro, MJ ;

Coughlin, SR .

BIOCHEMISTRY, 1999, 38 (29) :9308-9316

[9] Protease-activated receptor-1 can mediate responses to SFLLRN in thrombin-desensitized cells: Evidence for a novel mechanism for preventing or terminating signaling by PAR1's tethered ligand [J].

Hammes, SR ;

Coughlin, SR .

BIOCHEMISTRY, 1999, 38 (08) :2486-2493

[10]

HOLLENBERG MD, 1993, MOL PHARMACOL, V43, P921

← 1 2 3 →