![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
CC Chan, P Ecclestone, DW Nicholson, KM Metters, DJ Pon and IW Rodger
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada.
Agonist-induced changes in intracellular calcium ion concentration ([Ca++]i) were examined in human monocytic leukemia THP-1 cells loaded with fura 2/acetoxymethyl ester (fura 2/AM). Leukotriene (LT)D4 induced a concentration-dependent biphasic response consisting of a transient phase (up to 5-fold peak increase) followed by a sustained phase, showing characteristics of a receptor-operated calcium channel. Homologous desensitization to LTD4 was observed. The responses to LTD4 were reduced by 80 to 90% in calcium-free buffer. The responses to LTD4 in a calcium-free buffer were dependent upon the duration of prior exposure of the cells to a calcium-free environment. The response at 30 or 60 min after exposure to calcium-free buffer was greater than that at earlier time points (time-dependent sensitization). Similar responses were obtained with THP-1 cells exposed to EDTA-containing buffer. It is speculated that such time-dependent sensitization is a result of changes at the receptor level. The responses to LTD4 were blocked by two specific LTD4 antagonists, MK-0571 and ICI-204,219, in a concentration-dependent manner. When given after addition of LTD4, MK- 0571 or ICI-204,219 reversed the sustained phase of the LTD4-induced response, suggesting that maintenance of the response requires persistent activation of the LTD4 receptor. ICI-204,219 was 5 to 10 times more potent than MK-0571 (IC50 values of 1.1 and 9.3 nM, respectively), in agreement with results from radioligand binding studies reported separately.
This article has been cited by other articles:
|
|
 |
|
  I. Prinz, C. Gregoire, H. Mollenkopf, E. Aguado, Y. Wang, M. Malissen, S. H.E. Kaufmann, and B. Malissen The Type 1 Cysteinyl Leukotriene Receptor Triggers Calcium Influx and Chemotaxis in Mouse {alpha}{beta}- and {gamma}{delta} Effector T Cells J. Immunol., July 15, 2005; 175(2): 713 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Eum, K. Maghni, Q. Hamid, H. Campbell, D. H. Eidelman, and J. G. Martin Involvement of the Cysteinyl-Leukotrienes in Allergen-Induced Airway Eosinophilia and Hyperresponsiveness in the Mouse Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 25 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ogasawara, S. Ishii, T. Yokomizo, T. Kakinuma, M. Komine, K. Tamaki, T. Shimizu, and T. Izumi Characterization of Mouse Cysteinyl Leukotriene Receptors mCysLT1 and mCysLT2. DIFFERENTIAL PHARMACOLOGICAL PROPERTIES AND TISSUE DISTRIBUTION J. Biol. Chem., May 17, 2002; 277(21): 18763 - 18768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bautz, C. Denzlinger, L. Kanz, and R. Mohle Chemotaxis and transendothelial migration of CD34+ hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1 Blood, June 1, 2001; 97(11): 3433 - 3440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hoshino, T. Izumi, and T. Shimizu Leukotriene D4 Activates Mitogen-activated Protein Kinase through a Protein Kinase Calpha -Raf-1-dependent Pathway in Human Monocytic Leukemia THP-1 Cells J. Biol. Chem., February 27, 1998; 273(9): 4878 - 4882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. CALHOUN, B. J. LAVINS, M. C. MINKWITZ, R. EVANS, G. J. GLEICH, and J. COHN Effect of Zafirlukast (Accolate) on Cellular Mediators of Inflammation . Bronchoalveolar Lavage Fluid Findings after Segmental Antigen Challenge Am. J. Respir. Crit. Care Med., May 1, 1997; 157(5): 1381 - 1389. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Dumitriu, S. Prié, S. G. Bernier, G. Guillemette, and P. Sirois Mechanism of Action of Leukotriene D4 on Guinea Pig Tracheal Smooth Muscle Cells: Roles of Ca++ Influx and Intracellular Ca++ Release J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1357 - 1365. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Boie, N. Sawyer, D. M. Slipetz, K. M. Metters, and M. Abramovitz Molecular Cloning and Characterization of the Human Prostanoid DP Receptor J. Biol. Chem., August 11, 1995; 270(32): 18910 - 18916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. McMahon, C. Stenson, F. McPhillips, A. Fanning, H. R. Brady, and C. Godson Lipoxin A4 Antagonizes the Mitogenic Effects of Leukotriene D4 in Human Renal Mesangial Cells. DIFFERENTIAL ACTIVATION OF MAP KINASES THROUGH DISTINCT RECEPTORS J. Biol. Chem., September 1, 2000; 275(36): 27566 - 27575. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
