scholarly journals Involvement of thromboxane A2 in airway mucous cells in asthma-related cough

2002 ◽  
Vol 92 (2) ◽  
pp. 763-770 ◽  
Author(s):  
Anbo Xiang ◽  
Yoshiyuki Uchida ◽  
Akihiro Nomura ◽  
Hiroaki Iijima ◽  
Tohru Sakamoto ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Allergic Airway Inflammation ◽  
Thromboxane A2 ◽  
Lavage Fluid ◽  
Mucous Cells ◽  
Thromboxane Receptor ◽  
Neurokinin Receptor ◽  
Thromboxane Synthetase ◽  
Thromboxane Receptor Antagonist

The aim of this study was to elucidate the role of thromboxane A2 (TxA2) on asthma-related cough in guinea pigs. Animals were immunosensitized and repeatedly challenged with ovalbumin as an antigen. Coughs were induced by the inhalation of 10−5 M capsaicin solution for 10 min. Thromboxane synthetase (TxS) inhibitor OKY-046 and thromboxane-receptor antagonist AA-2414 significantly inhibited cough responses in repeatedly challenged animals. Inhalation of TxA2 mimic STA-2- potentiated cough responses in normal and immunosensitized animals but not in repeatedly challenged ones. Moreover, STA-2-potentiated coughs were inhibited by administration of neurokinin-receptor antagonist FK-224. In repeatedly challenged animals, concentration of TxB2 in airway lavage fluid, expression of TxS mRNA in tracheal epithelia, and the immunostaining intensity against TxS in mucous cells of the epithelium significantly increased compared with normal and sensitized animals. These results suggest that TxA2 derived from mucous cells potentiated cough responses to capsaicin in allergic airway inflammation.

Do Thromboxane-Sensitive Receptors Mediate Platelet Aggregation In The Rat?

1981 ◽  
Author(s):  
G G Duncan ◽  
G M Smith
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Thromboxane Receptor ◽  
Competitive Antagonism ◽  
Conflicting Evidence ◽  
Thromboxane Synthetase ◽  
Thromboxane Receptor Antagonist ◽  
Induced Aggregation

Evidence has been produced to suggest that platelets of rabbits and humans contain receptors sensitive to thromboxane A2 (TxA2) and that inhibition of platelet aggregation can be achieved by preventing the conversion of the cyclo endoperoxides to TxA2 or by competitive antagonism of TxA2 at these TxA2-sensitive receptors. Conflicting evidence has been published on the possible role of TxA2 in the rat and this communication will attempt to explain the effects of agonists and inhibitors in rats and rabbits.Platelet aggregation was measured in vivo by continuously measuring the circulating platelet count using the Technicon Auto-counter. Collagen, PGH2 and the synthetic prostanoids U446l9 and U44069 were studied in rats and collagen and PGH2 were also studied in rabbits. The effects of cyclo-oxygenase inhibitors, thromboxane synthetase inhibitors and thromboxane receptor antagonists on aggregation produced by collagen and PGH2 were studied. Collagen, U44069 and PGH2 produced a dose-dependent fall in platelet count in rats. U46619 was inactive at nontoxic doses. Cyclo-oxygenase inhibitors partially inhibited collagen-induced aggregation in both rats and rabbits. 1-n-butylimidazole (25 mg/kg) and phthalazinol (1 mg/kg) (reported to be a thromboxane receptor antagonist) both inhibited aggregation produced by collagen and PGH2 in the rabbit but they did not affect aggregation produced by collagen in the rat.The activity of the cyclo-oxygenase inhibitors suggests that collagen-induced aggregation is partially mediated by products of arachidonic acid in rats and rabbits but evidence that the conversion of PGH2 to TxA2 is necessary for aggregation to be produced in rats by this pathway could not be obtained.

Blockade of thromboxane responses in the airway of the cat by SQ 29,548

1987 ◽  
Vol 62 (6) ◽  
pp. 2193-2200 ◽  
Author(s):  
D. C. Underwood ◽  
T. Kriseman ◽  
D. B. McNamara ◽  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Receptor Antagonist ◽  
Thromboxane A2 ◽  
Transpulmonary Pressure ◽  
Dynamic Compliance ◽  
Systemic Arterial Pressure ◽  
Pure Substance ◽  
Thromboxane Receptor ◽  
Airway Response ◽  
Airway Responses ◽  
Thromboxane Receptor Antagonist

The effects of SQ 29,548, a thromboxane receptor antagonist, on airway responses were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of the thromboxane and prostaglandin precursor, arachidonic acid (AA), and the thromboxane mimic, U 46619, produced dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic compliance. After administration of SQ 29,548 (0.5 mg/kg iv), bronchoconstrictor responses to AA were reduced by approximately 50%, whereas responses to U 46619 were reduced by approximately 90%. The cyclooxygenase inhibitor, sodium meclofenamate (2.5 mg/kg iv), blocked the component of the airway response to AA remaining after treatment with SQ 29,548. The thromboxane receptor antagonist had no significant effect on bronchoconstrictor responses to prostaglandins F2 alpha, and D2, methacholine, 5-hydroxytryptamine, histamine, or BAY K 8644, an agent that promotes calcium entry. Reductions in systemic arterial pressure in response to AA were enhanced by the thromboxane receptor antagonist and abolished by meclofenamate. SQ 29,548 had no effect on terminal enzyme activity in microsomal fractions from cat lung. These data support the hypothesis that AA-induced bronchoconstriction in the cat is mediated in large part by the actions of thromboxane A2. These data also suggest that U 46619 and U 44069 stimulate the same airway receptor as thromboxane A2 and mimic the bronchomotor effects of this hormone, which has not yet been isolated as a pure substance. These data demonstrate that SQ 29,548 is a selective thromboxane receptor antagonist in the airways of the closed-chest cat and may be a useful probe for studying responses to thromboxane A2 in physiological and pathophysiological processes in the lung.

Synergistic Antiplatelet Effect of Ridogrel, a Combined Thromboxane Receptor Antagonist and Thromboxane Synthase Inhibitor, and UDCG-212, a cAMP-Phosphodiesterase Inhibitor

1993 ◽  
Vol 70 (05) ◽  
pp. 822-825 ◽  
Author(s):  
B Hoet ◽  
J Arnout ◽  
H Deckmyn ◽  
J Vermylen
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Phosphodiesterase Inhibitor ◽  
Camp Phosphodiesterase ◽  
Thromboxane Receptor ◽  
Thromboxane Synthase Inhibitor ◽  
Thromboxane Receptor Antagonist ◽  
Synthase Inhibitor ◽  
Camp Levels

SummaryRidogrel, a combined thromboxane receptor antagonist and thromboxane synthase inhibitor (1), inhibits platelet aggregation. Following stimulation with arachidonic acid, cAMP-levels are increased in human platelets preincubated with ridogrel, this is due to the known reorientation of the metabolism of the formed endoperoxides towards adenylate cyclase stimulating prostaglandins.Pretreatment of resting platelets with UDCG-212, a cAMP-phosphodiesterase inhibitor (2), also inhibits platelet aggregation induced by arachidonic acid, concomitant with an increase in cAMP levels, due to an inhibition of its breakdown. Under basal conditions, cAMP also is increased.By combining the two drugs, a more than additive action was observed on platelet aggregation and on both resting and stimulated platelet cAMP content. The appropriate combination may result in a more effective antiplatelet strategy.

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