![[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}
|
|
|
|
|
||
L Furci, DJ Fitzgerald and GA Fitzgerald
Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee.
Studies of the hierarchies of agonist and antagonist affinity for the prostaglandin (PG)H2/thromboxane (Tx)A2 receptor have been performed to establish whether distinct receptor subtypes exist in platelets and vascular smooth muscle cells (VSMC). They have yielded conflicting results. The pattern of homologous desensitization of phospholipase C activation and [Ca++i] increase induced by the PGH2/TxA2 agonist U46619 in rat aortic SMC was similar to that previously observed in human platelets: rapid desensitization of both responses followed by a delayed loss of binding sites from the cell membrane. Recently, the pattern of receptor inactivation by the antagonist ligand, GR 32191, has identified two subtypes in platelets. GR 32191 binds reversibly (GRr) to a site that mediates platelet shape change and an increase [Ca++i] and irreversibly (GRirr) to a site linked to phospholipase C activation and aggregation. In contrast to platelets, studies of ligand dissociation only identified GRr sites in rat aortic SMC and GR 32191 failed to inactivate PGH2/TxA2 receptors as detected by the PGH2/TxA2 receptor antagonist, [3H]SQ 29548. Inhibition of U46619-induced contraction of both rat aortic and human saphenous vein was competitive, consistent with the absence of GRirr sites in VSMC. Platelet activating factor, which heterologously desensitizes U46619- evoked phospholipase C activation in platelets, had no such effect in VSMC. The biochemical events attendant to PGH2/TxA2 receptor desensitization are similar in SMC and platelets. However, both the pattern of receptor inactivation by GR 32191 and of heterologous desensitization by PAF, suggest that VSMC lack the receptor subtype that transduces aggregation of platelets.
This article has been cited by other articles:
|
|
 |
|
  L.-W. Fu, Z.-L. Guo, and J. C. Longhurst Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia J. Physiol., July 1, 2008; 586(13): 3287 - 3300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Thomas, P. N. Rocha, C. Nataraj, L. A. Robinson, R. F. Spurney, B. H. Koller, and T. M. Coffman Proinflammatory Actions of Thromboxane Receptors to Enhance Cellular Immune Responses J. Immunol., December 15, 2003; 171(12): 6389 - 6395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M Vila, J. B Martinez-Leon, P. Medina, G. Segarra, R. M Ballester, E. Otero, and S. Lluch U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade Cardiovasc Res, December 1, 2001; 52(3): 462 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tosun, R. J. Paul, and R. M. Rapoport Role of Extracellular Ca++ Influx via L-Type and Non-L-Type Ca++ Channels in Thromboxane A2 Receptor-Mediated Contraction in Rat Aorta J. Pharmacol. Exp. Ther., March 1, 1998; 284(3): 921 - 928. [Abstract] [Full Text]
|
|
|
|
|
|
B. Askari, C. P. Bell-Quilley, D. Fulton, J. Quilley, and J. C. McGiff Analysis of Eicosanoid Mediation of the Renal Functional Effects of Hyperchloremia, J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 101 - 107. [Abstract] [Full Text]
|
|
|
|
|
|
B. T. Kinsella, D. J. O'Mahony, and G. A. Fitzgerald The Human Thromboxane A2 Receptor alpha Isoform (TPalpha ) Functionally Couples to the G Proteins Gq and G11 In Vivo and is Activated by the Isoprostane 8-epi Prostaglandin F2alpha J. Pharmacol. Exp. Ther., May 1, 1997; 281(2): 957 - 964. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Habib, R. Vezza, C. Creminon, J. Maclouf, and G. A. FitzGerald Rapid, Agonist-dependent Phosphorylation in Vivo of Human Thromboxane Receptor Isoforms. MINIMAL INVOLVEMENT OF PROTEIN KINASE C J. Biol. Chem., March 14, 1997; 272(11): 7191 - 7200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pratico, E. M. Smyth, F. Violi, and G. A. FitzGerald Local Amplification of Platelet Function by 8-Epi Prostaglandin F2alpha Is Not Mediated by Thromboxane Receptor Isoforms J. Biol. Chem., June 21, 1996; 271(25): 14916 - 14924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pratico and G. A. FitzGerald Testosterone and Thromboxane : Of Muscles, Mice, and Men Circulation, June 1, 1995; 91(11): 2694 - 2698. [Full Text]
|
|
|
|
|
|
D. Pratico, J. A. Lawson, and G. A. FitzGerald Cylooxygenase-dependent Formation of the Isoprostane, 8-Epi Prostaglandin F[IMAGE] J. Biol. Chem., April 28, 1995; 270(17): 9800 - 9808. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
