Exploring the pharmacology of the leukotriene B-4 receptor BLT1, without the confounding effects of BLT2

Research output: Contribution to journalArticle

Abstract

Most previous studies of leukotriene B-4 (LTB4) pharmacology using primary leukocyte cultures and myeloid cell lines do not differentiate between leukotriene BLT1 and BLT1 receptor activation because both receptors are often expressed by these cells. Here we show that in HeLa cells expressing BLT1 but not BLT2 receptors, BLT1 receptor activation resulted in IP3 mediated calcium release from intracellular stores initially, followed by calcium influx through cell membrane channels. BLT1 calcium signalling was sensitive to the activity of protein kinase C (PKC). protein kinase A (PKA) and protein-tyrosine kinases (PTKs), as well as changes in membrane cholesterol levels and treatments that are known to disrupt normal membrane physiology and/or lipid rafts. Inhibition of MAP kinases, Rho-associated kinases, or phosphomositol-3-kinases (PI3K) had no effect on BLT1 receptor induced calcium signalling, and the receptor was insensitive to the redox state of the extracellular compartment. (C) 2004 Elsevier B.V. All rights reserved.

Details

Authors
  • Alan Sabirsh
  • Jesper Bristulf
  • Christer Owman
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology

Keywords

  • fura-2, BLT1, leukotriene B-4, g-protein coupled receptor, pharmacology, calcium
Original languageEnglish
Pages (from-to)53-65
JournalEuropean Journal of Pharmacology
Volume499
Issue number1-2
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes