論文

査読有り
2008年6月

Down-regulation of histamine H(1) receptors by beta(2)-adrenoceptor-mediated inhibition of H(1) receptor gene transcription

JOURNAL OF PHARMACY AND PHARMACOLOGY
  • Katsuhiro Miyoshi
  • ,
  • Nozomi Kawakami
  • ,
  • Hayato Umehara
  • ,
  • Katsumi Fujimoto
  • ,
  • Shuhei Horio
  • ,
  • Hiroyuki Fukui

60
6
開始ページ
747
終了ページ
752
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1211/jpp.60.6.0010
出版者・発行元
WILEY-BLACKWELL

Histamine H(1) receptor (H1R) levels vary under various pathological conditions, and these changes may be responsible for some pathogenesis such as in allergic rhinitis. Several stimulants, including histamine, muscarinic agonists and platelet-activating factor, have now been shown to regulate H1R levels and may have roles in regulating the H1R level in physiological and pathological conditions. Results for beta(2)-adrenoceptor (beta 2AR) stimulation are conflicting, however. beta 2AR up-regulated H1R in bovine tracheal smooth muscle, but down-regulated human H1R expressed in Chinese hamster ovary (CHO) cells. It is possible that this discrepancy comes from the differences in the preparations used for each study: the former cell expressed bovine H1R and the latter cell expressed human H1R. Moreover, CHO cells have been shown to be inadequate for studying the effects on H1R gene expression, because the cells express non-endogenous stably transfected H1R under the control of the SV40 promoter. Therefore, in this study, we have investigated the role of beta 2AR stimulation in H1R gene regulation using human U373 astrocytoma cells that express endogenous H1R and transfected beta 2AR. Stimulation of beta 2AR significantly reduced H1R promoter activity and H1R mRNA levels. H1R mRNA stability was slightly reduced by beta 2AR stimulation, although this was not significant. The decrease of H1R mRNA by beta 2AR stimulation was blocked by the protein kinase A (PKA) inhibitor KT5720, suggesting the involvement of PKA. These results indicate that the beta 2AR is involved in the down-regulation of human H1R by inhibiting H1R gene transcription through a PKA-dependent process.


リンク情報
DOI
https://doi.org/10.1211/jpp.60.6.0010
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/18498711
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000256240200010&DestApp=WOS_CPL
ID情報
  • DOI : 10.1211/jpp.60.6.0010
  • ISSN : 0022-3573
  • PubMed ID : 18498711
  • Web of Science ID : WOS:000256240200010

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