Abstract
We measured the effects of stable thromboxane A2 (TXA2) analogues on signalling in cultured human myometrial cells. U46619 and/or IBOP stimulated total inositol phosphates (IPs) and cAMP production, RhoA-associated protein kinase (ROK) activity and elevated intracellular calcium [Ca2+]i. Pretreatment of the cells with pertussis toxin did not inhibit IPs or [Ca2+]i production but the thromboxane receptor (TP) antagonist SQ-29548 did inhibit IPs and cAMP production, the elevation of [Ca2+]i, and the increase in ROK activity. Pretreatment with thapsigargin inhibited [Ca2+]i elevation. TP receptor-stimulated ROK activity was inhibited by the ROK inhibitor Y27632 while ROK activity was enhanced by the caspase 3 inhibitor, Z-DEVD-FMK. TP receptor-stimulated IPs production is additive to prostaglandin F2alpha (FP) or prostaglandin E (EP) receptor-stimulated IPs production and neither FP nor EP receptor-stimulated IPs production is inhibited by SQ29548. Thus cultured human myometrial cells express at least two functional TP receptor subtypes; TPalpha-like (cAMP-stimulating) and TPbeta-like (IPs, [Ca2+] and ROK-stimulating).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
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Amides / pharmacology
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Amino Acid Sequence
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Bridged Bicyclo Compounds, Heterocyclic
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Calcium / metabolism
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Caspase 3
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Caspase Inhibitors
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Cells, Cultured
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Cyclic AMP / metabolism
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Enzyme Inhibitors / pharmacology
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Fatty Acids, Unsaturated
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Female
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Humans
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Hydrazines / pharmacology
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Intracellular Signaling Peptides and Proteins
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Molecular Sequence Data
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Myometrium / cytology
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Myometrium / drug effects
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Myometrium / metabolism*
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Oligopeptides / pharmacology
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Protein Isoforms
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism
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Pyridines / pharmacology
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Receptors, Thromboxane / drug effects
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Receptors, Thromboxane / metabolism*
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Signal Transduction*
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Type C Phospholipases / drug effects
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Type C Phospholipases / metabolism
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rho-Associated Kinases
Substances
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Amides
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Bridged Bicyclo Compounds, Heterocyclic
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Caspase Inhibitors
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Enzyme Inhibitors
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Fatty Acids, Unsaturated
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Hydrazines
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Intracellular Signaling Peptides and Proteins
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Oligopeptides
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Protein Isoforms
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Pyridines
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Receptors, Thromboxane
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benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
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Y 27632
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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SQ 29548
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Cyclic AMP
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Protein Serine-Threonine Kinases
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rho-Associated Kinases
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Type C Phospholipases
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CASP3 protein, human
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Caspase 3
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Calcium