Epinephrine correction of impaired platelet thromboxane receptor signaling

Patricia C. Dunlop, Linda A. Leis, Gerhard J. Johnson

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

This study evaluated the mechanism of epinephrine potentiation of platelet secretion induced by thromboxane A2 (TXA2). Dog platelets that do not secrete in response to TXA2 alone (TXA2-) were compared with dog platelets that do secrete (TXA2+) and with human platelets. TXA2- platelets had impaired TXA2 receptor (TP receptor)-G protein coupling, indicated by 1) impaired stimulated GTPase activity, 2) elevated basal guanosine 5'-O-(3-thiotriphosphate) binding, and 3) elevated Gα(q) palmitate turnover that was corrected by preexposure to epinephrine. Kinetic agonist binding studies revealed biphasic dog and human platelet TP receptor association and dissociation. TXA2- and TP receptor-desensitized TXA2+ dog and human platelets had altered ligand binding parameters compared with untreated TXA2+ or human platelets. These parameters were reversed, along with impaired secretion, by epinephrine. Basal phosphorylation of TXA2- platelet TP receptors was elevated 60% and was normalized by epinephrine. Epinephrine potentiates platelet secretion stimulated by TXA2 by reducing basal TP receptor phosphorylation and facilitating TP receptor-G protein coupling in TXA2- platelets and, probably, in normal platelets as well.

Original languageEnglish (US)
Pages (from-to)C1760-C1771
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number6 48-6
DOIs
StatePublished - 2000

Keywords

  • Dogs
  • G proteins
  • Platelet activation

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