Regulation of inducible bradykinin B1 receptor gene expression through absence of internalization and resensitization
Regulation of inducible bradykinin B1 receptor gene expression through absence of internalization and resensitization
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DOI：
10.1002/1097-4644(20000901)78:3
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发表时间：
2000-06-01
影响因子：
4
通讯作者：
Polgar, P
中科院分区：
文献类型：
--
作者：
Zhou, XF;Prado, GN;Polgar, P
Rapid induction and down-regulation of bradykinin B1 receptor (BKB1R) gene expression is tightly regulated at the transcriptional and mRNA levels (Zhou et al. [1998] Biochem. J. 330:361-366; Zhou et at. [1999] Mel. Cell Biol. Res. Commun. 1:29-35). Here we explore regulation of BKB1R expression at the protein level. To make this inducible gene express constitutively, we utilized a bicistronic mammalian expression vector (pCMin) for stable transfection of the BKB1R gene into human lung fibroblasts, IMR90SV40. The BKB1R displayed a high affinity and specificity (K-d = 0.5 nM) for desArg(10)-kallidin. The receptor mediated such signaling events as arachidonic acid (ARA) release, phosphoinositide (PI) turnover and Ca2+-flux. The receptor function proved differentially desensitized. For example, after initial exposure to desArg(10)-kallidin, a second stimulation with desArg(10)-kallidin did not induce further Ca2+-flux or ARA-release while PI-turnover continued unabated. Unlike most of the C-protein coupled receptors, the BKB1R did not internalize within 60 min of exposure to 10 nM desArg(10)-kallidin. It also did not resensitize. Thus, the duration and signal capacity of the BKB1R at the protein level is regulated through lack of internalization, an absence of resensitization and a lack of desensitization for certain events such as PI turnover. In fact, the absence of BKB1R resensitization Is likely a very important contributor to the rapid disappearance of this inducible receptor. (C) 2000 Wiley-Liss, Inc.
