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Up-Regulation of G-Protein-Coupled Receptors for Endothelin and Thromboxane by Lipid-Soluble Smoke Particles in Renal Artery of Rat

Xie, Yan-hua; Wang, Si-wang; Zhang, Yaping; Edvinsson, Lars LU and Xu, Cang-Bao LU (2010) In Basic & Clinical Pharmacology & Toxicology2004-01-01+01:002014-01-01+01:00 107(4). p.803-812
Abstract
Up-regulation of G-protein-coupled receptors (GPCR) plays key roles in renal hypertension and cardiovascular disease pathogenesis. The present study was designed to examine if lipid-soluble cigarette smoking particles (DSP), nicotine and endotoxin (LPS), induce GPCR up-regulation for thromboxane A(2) (TP), endothelin type A (ETA) and type B (ETB) receptors in renal artery, and if intracellular signal mechanisms are involved. Renal artery segments of rats were exposed to DSP, nicotine or LPS, in organ culture for up to 24 hr. The GPCR-mediated contractions were recorded by using a myograph system. Expression of the GPCR was examined by real-time PCR and immunohistochemistry at mRNA and protein levels. Sarafatoxin 6c (S6c, selective ETB... (More)
Up-regulation of G-protein-coupled receptors (GPCR) plays key roles in renal hypertension and cardiovascular disease pathogenesis. The present study was designed to examine if lipid-soluble cigarette smoking particles (DSP), nicotine and endotoxin (LPS), induce GPCR up-regulation for thromboxane A(2) (TP), endothelin type A (ETA) and type B (ETB) receptors in renal artery, and if intracellular signal mechanisms are involved. Renal artery segments of rats were exposed to DSP, nicotine or LPS, in organ culture for up to 24 hr. The GPCR-mediated contractions were recorded by using a myograph system. Expression of the GPCR was examined by real-time PCR and immunohistochemistry at mRNA and protein levels. Sarafatoxin 6c (S6c, selective ETB receptor agonist), endothelin-1 (ET-1, non-selective ETA and ETB receptor agonist) and 9,11-Dideoxy-9a,11a-methanoepoxy prostaglandin F-2a (U46619, a TP receptor agonist) induced contractions were significantly increased after the arterial segments exposed to DSP in a concentration-dependent (0.1-0.4 mu l/ml) manner, and S6c also induced a time-dependent contraction, compared to control (dimethyl sulfoxide). This was in parallel with enhanced mRNA expression for ETB receptor but not ETA and TP receptors, while increased protein expression for ETA, ETB and TP receptors was seen. The specific nuclear factor-kappa B (NF-kappa B) signal pathway inhibitor BMS345541 was applied to link DSP effects to the GPCR up-regulation. It totally abolished ETB receptor up-regulation, but not ETA and TP receptor up-regulations. Our results suggest that DSP transcriptionally up-regulated ETB receptor expression in rat renal artery via NF-kappa B signal pathways, whereas up-regulation of ETA and TP receptor-mediated contraction may involve post-transcriptional mechanisms. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Basic & Clinical Pharmacology & Toxicology2004-01-01+01:002014-01-01+01:00
volume
107
issue
4
pages
803 - 812
publisher
Wiley-Blackwell
external identifiers
  • wos:000281834300006
  • scopus:77956813903
ISSN
1742-7843
DOI
10.1111/j.1742-7843.2010.00585.x
language
English
LU publication?
yes
id
d8febac7-cdd2-47f7-896d-b509527f0568 (old id 1728145)
date added to LUP
2010-11-22 13:53:47
date last changed
2018-05-29 11:39:12
@article{d8febac7-cdd2-47f7-896d-b509527f0568,
  abstract     = {Up-regulation of G-protein-coupled receptors (GPCR) plays key roles in renal hypertension and cardiovascular disease pathogenesis. The present study was designed to examine if lipid-soluble cigarette smoking particles (DSP), nicotine and endotoxin (LPS), induce GPCR up-regulation for thromboxane A(2) (TP), endothelin type A (ETA) and type B (ETB) receptors in renal artery, and if intracellular signal mechanisms are involved. Renal artery segments of rats were exposed to DSP, nicotine or LPS, in organ culture for up to 24 hr. The GPCR-mediated contractions were recorded by using a myograph system. Expression of the GPCR was examined by real-time PCR and immunohistochemistry at mRNA and protein levels. Sarafatoxin 6c (S6c, selective ETB receptor agonist), endothelin-1 (ET-1, non-selective ETA and ETB receptor agonist) and 9,11-Dideoxy-9a,11a-methanoepoxy prostaglandin F-2a (U46619, a TP receptor agonist) induced contractions were significantly increased after the arterial segments exposed to DSP in a concentration-dependent (0.1-0.4 mu l/ml) manner, and S6c also induced a time-dependent contraction, compared to control (dimethyl sulfoxide). This was in parallel with enhanced mRNA expression for ETB receptor but not ETA and TP receptors, while increased protein expression for ETA, ETB and TP receptors was seen. The specific nuclear factor-kappa B (NF-kappa B) signal pathway inhibitor BMS345541 was applied to link DSP effects to the GPCR up-regulation. It totally abolished ETB receptor up-regulation, but not ETA and TP receptor up-regulations. Our results suggest that DSP transcriptionally up-regulated ETB receptor expression in rat renal artery via NF-kappa B signal pathways, whereas up-regulation of ETA and TP receptor-mediated contraction may involve post-transcriptional mechanisms.},
  author       = {Xie, Yan-hua and Wang, Si-wang and Zhang, Yaping and Edvinsson, Lars and Xu, Cang-Bao},
  issn         = {1742-7843},
  language     = {eng},
  number       = {4},
  pages        = {803--812},
  publisher    = {Wiley-Blackwell},
  series       = {Basic & Clinical Pharmacology & Toxicology2004-01-01+01:002014-01-01+01:00},
  title        = {Up-Regulation of G-Protein-Coupled Receptors for Endothelin and Thromboxane by Lipid-Soluble Smoke Particles in Renal Artery of Rat},
  url          = {http://dx.doi.org/10.1111/j.1742-7843.2010.00585.x},
  volume       = {107},
  year         = {2010},
}