Exploring the pharmacology of the leukotriene B4 receptor BLT1, without the confounding effects of BLT2

• Published in: European journal of pharmacology Vol. 499; no. 1-2; pp. 53 - 65
• Main Authors: SABIRSH, Alan, BRISTULF, Jesper, OWMAN, Christer
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 19.09.2004
• Subjects: Biological and medical sciences; Boron Compounds - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cytosol - drug effects; Cytosol - metabolism; Dantrolene - pharmacology; Dose-Response Relationship, Drug; Estrenes - pharmacology; Fatty Alcohols - pharmacology; Glycols - pharmacology; HeLa Cells; Humans; Imidazoles - pharmacology; Indoles - pharmacology; Intracellular Space - drug effects; Intracellular Space - metabolism; Maleimides - pharmacology; Medical sciences; Medicin och hälsovetenskap; Nickel - pharmacology; Nifedipine - pharmacology; Pharmacology. Drug treatments; Plasmids - genetics; Propranolol - pharmacology; Protein Kinase Inhibitors - pharmacology; Pyrrolidinones - pharmacology; Receptors, Leukotriene B4 - genetics; Receptors, Leukotriene B4 - metabolism; Staurosporine - pharmacology; Tetradecanoylphorbol Acetate - pharmacology; Thapsigargin - pharmacology; Transfection; Calcium; Leukotriene receptor; Arachidonic acid derivatives; Pharmacology; Inorganic element; Leukotriene; G-protein coupled receptor; Leukotriene B4; Eicosanoid; BLT1; Fura-2; G protein; Biological receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.07.060

Most previous studies of leukotriene B4 (LTB4) pharmacology using primary leukocyte cultures and myeloid cell lines do not differentiate between leukotriene BLT1 and BLT2 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 phosphoinositol-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.