豚鼠半胱氨酰白三烯受体2（gpCysLT2）通过LTC4和LTD4介导细胞增殖和细胞内钙动员。

Guinea pig cysteinyl leukotriene receptor 2 (gpCysLT2) mediates cell proliferation and intracellular calcium mobilization by LTC4 and LTD4.

作者信息

Ito Yoshiyuki, Hirano Minoru, Umemoto Noriko, Zang Liqing, Wang Zhipeng, Oka Takehiko, Shimada Yasuhito, Nishimura Yuhei, Kurokawa Ichiro, Mizutani Hitoshi, Tanaka Toshio

机构信息

Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University, Tsu, Japan.

出版信息

BMB Rep. 2008 Feb 29;41(2):139-45. doi: 10.5483/bmbrep.2008.41.2.139.

DOI:10.5483/bmbrep.2008.41.2.139

PMID:18315950

Abstract

We cloned and pharmacologically characterized the guinea pig cysteinyl leukotriene (CysLT) 2 receptor (gpCysLT2). gpCysLT2 consists of 317 amino acids with 75.3%, 75.2%, 73.3% identity to those of humans, mice and rats, respectively. The gpCysLT2 gene is highly expressed in the lung, moderately in eosinophils, skin, spleen, stomach, colon, and modestly in the small intestine. CysLTs accelerated the proliferation of gpCysLT2-expressing HEK293. Leukotriene C4 (LTC4) and Leukotriene D4 (LTD4) enhanced the cell proliferation higher than Bay-u9773, a CysLT2 selective partial agonist and a nonselective antagonist for CysLT receptors. Bay-u9773 did not antagonize the cell proliferation by LTC4 and LTD4. Despite the equipotency of the mitogenic effect among these chemicals, calcium mobilization (CM) levels were variable (LTC4> LTD4>> Bay-u9773), and Bay-u9773 antagonized the CM by LTC4. Moreover, the Gi/o inhibitor pertussis toxin perfectly inhibited agonist-induced cell proliferation. These results reveal that cell proliferation via CysLT2 signaling was mediated by Gi/o signaling but independent of calcium mobilization.

摘要

我们克隆了豚鼠半胱氨酰白三烯（CysLT）2受体（gpCysLT2）并对其进行了药理学特性分析。gpCysLT2由317个氨基酸组成，与人类、小鼠和大鼠的CysLT2分别具有75.3%、75.2%和73.3%的同源性。gpCysLT2基因在肺中高度表达，在嗜酸性粒细胞、皮肤、脾脏、胃、结肠中中度表达，在小肠中表达较弱。CysLTs促进了表达gpCysLT2的HEK293细胞的增殖。白三烯C4（LTC4）和白三烯D4（LTD4）比CysLT2选择性部分激动剂和CysLT受体非选择性拮抗剂Bay-u9773更能增强细胞增殖。Bay-u9773不能拮抗LTC4和LTD4引起的细胞增殖。尽管这些化学物质的促有丝分裂作用效价相同，但钙动员（CM）水平各不相同（LTC4 > LTD4 >> Bay-u9773），且Bay-u9773能拮抗LTC4引起的CM。此外，Gi/o抑制剂百日咳毒素能完全抑制激动剂诱导的细胞增殖。这些结果表明，通过CysLT2信号传导的细胞增殖是由Gi/o信号传导介导的，但与钙动员无关。