Platelet Thromboxane Receptors: Biology and Function

Johnson, Gerhard J.

doi:10.1007/978-1-4615-5049-5_3

Handbook of Platelet Physiology and Pharmacology 1999

DOI: 10.1007/978-1-4615-5049-5_3

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Platelet Thromboxane Receptors: Biology and Function

Gerhard J. Johnson¹

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2000

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“…TP receptors belong to the family of G protein-coupled receptors (GPCRs) that activate effectors via G proteins (16). Agonist binding to platelet TP receptors activates G␣ 13 , which results in platelet shape change (24), and G␣ q , which in turn activates PLC ␤-isoforms (PLC-␤) (3,19,17,34). Activation of PLC-␤ liberates two important intracellular messengers: D-myo-inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol (DG).…”

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Epinephrine correction of impaired platelet thromboxane receptor signaling

Dunlop

Leis

Johnson

2000

American Journal of Physiology-Cell Physiology

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This study evaluated the mechanism of epinephrine potentiation of platelet secretion induced by thromboxane A(2) (TXA(2)). Dog platelets that do not secrete in response to TXA(2) alone (TXA(2)-) were compared with dog platelets that do secrete (TXA(2)+) and with human platelets. TXA(2)- platelets had impaired TXA(2) 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 Galpha(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. TXA(2)- and TP receptor-desensitized TXA(2)+ dog and human platelets had altered ligand binding parameters compared with untreated TXA(2)+ or human platelets. These parameters were reversed, along with impaired secretion, by epinephrine. Basal phosphorylation of TXA(2)- platelet TP receptors was elevated 60% and was normalized by epinephrine. Epinephrine potentiates platelet secretion stimulated by TXA(2) by reducing basal TP receptor phosphorylation and facilitating TP receptor-G protein coupling in TXA(2)- platelets and, probably, in normal platelets as well.

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confidence: 99%

Epinephrine correction of impaired platelet thromboxane receptor signaling

Dunlop

Leis

Johnson

2000

American Journal of Physiology-Cell Physiology

Self Cite

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Platelet Thromboxane Receptors: Biology and Function

Cited by 1 publication

References 199 publications

Epinephrine correction of impaired platelet thromboxane receptor signaling

Epinephrine correction of impaired platelet thromboxane receptor signaling

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