AJP - Renal Physiology, Vol 267, Issue 3 467-F478, Copyright © 1994 by American Physiological Society

ARTICLES

Modulation of thromboxane receptor activation in rat glomerular mesangial cells

R. F. Spurney, J. P. Middleton, J. R. Raymond and T. M. Coffman
Department of Medicine, Duke University, Durham, North Carolina.

Rat glomerular mesangial cells were used to investigate mechanisms of thromboxane A2 (TxA2) receptor regulation in the kidney. Exposure of mesangial cells to the TxA2 agonist U-46619 for 10 min reduced subsequent TxA2-induced increases in inositol phosphates and intracellular Ca2+ levels by approximately 70%. This loss of receptor responsiveness could be blocked by the TxA2 receptor antagonist SQ-29548 and was reversible after removal of agonist from the incubation medium. Radioligand binding studies using the TxA2 agonist [125I]BOP suggested that exposure of mesangial cells to U-46619 for 10 min reduced TxA2 receptor responsiveness without a loss of receptor sites from plasma membrane fractions of the cell, although the density of mesangial cell TxA2 receptors was decreased by approximately 60% after more prolonged exposure of mesangial cells to thromboxane agonists. Both desensitization to U-46619 and loss of TxA2 binding sites could be attenuated by the protein kinase C (PKC) inhibitors staurosporine, sphingosine, or H-7, and TxA2 receptor responsiveness was reduced in cells incubated with phorbol esters before stimulation with thromboxane agonists. We conclude that 1) agonist-specific decreases in TxA2 receptor responsiveness may involve initial uncoupling of the receptor from its effector systems, followed by a loss of TxA2 receptor sites from plasma membrane fractions of the cell, and 2) PKC may be involved in these processes.

This article has been cited by other articles:

				J. D. Imig Eicosanoid regulation of the renal vasculature Am J Physiol Renal Physiol, December 1, 2000; 279(6): F965 - F981. [Abstract] [Full Text] [PDF]

				J.-L. Parent, P. Labrecque, M. J. Orsini, and J. L. Benovic Internalization of the TXA2 Receptor alpha  and beta  Isoforms. ROLE OF THE DIFFERENTIALLY SPLICED COOH TERMINUS IN AGONIST-PROMOTED RECEPTOR INTERNALIZATION J. Biol. Chem., March 26, 1999; 274(13): 8941 - 8948. [Abstract] [Full Text] [PDF]

				T. M. Coffman, R. F. Spurney, R. B. Mannon, and R. Levenson Thromboxane A2 modulates the fibrinolytic system in glomerular mesangial cells Am J Physiol Renal Physiol, August 1, 1998; 275(2): F262 - F269. [Abstract] [Full Text] [PDF]

				A. A. Nanji, A. Rahemtulla, L. Maio, S. Khwaja, S. Zhao, S. R. Tahan, and P. Thomas Alterations in Thromboxane Synthase and Thromboxane A2 Receptors in Experimental Alcoholic Liver Disease J. Pharmacol. Exp. Ther., August 1, 1997; 282(2): 1037 - 1043. [Abstract] [Full Text]

				J.-L. Parent, P. Labrecque, M. Driss Rochdi, and J. L. Benovic Role of the Differentially Spliced Carboxyl Terminus in Thromboxane A2 Receptor Trafficking. IDENTIFICATION OF A DISTINCT MOTIF FOR TONIC INTERNALIZATION J. Biol. Chem., March 2, 2001; 276(10): 7079 - 7085. [Abstract] [Full Text] [PDF]