Study Progress in Signaling through Thromboxane A2 Receptors in Platelet and Anti-platelet Drugs / 中国药师

Thromboxane A2 receptors (TPs) widely distribute in different organ systems and localize both on cell membranes and in intracellular structures.TPs are the members of seven-transmembrane G-protein-coupled receptor (GPCR) super family.Historical-ly, the involvement of TPs in platelet functions has received the greatest attention .TPs have the capacity to activate different signaling cascades which regulate platelet shape change , aggregation and secretion response .Currently , anti-platelet drugs primarily act on re-ceptors and /or signaling molecules in activation pathways .The signaling transduction of TPs in platelet contributes to the investigation of the effects of extracts of traditional Chinese medicine on antiplatelet aggregation and the exploration of the action mechanisms .

Efficacy of Seratrodast, a Thromboxane A2 Receptor Inhibitor in a Double Blind Comparative Clinical Trial with Monteluklast.

Aims: To assess the comparative efficacy, safety and tolerability of seratrodast versus montelukast in controlling mild to moderate asthma in adult patients. Study Design: Randomized, comparative, double blind, double dummy, multi-center, parallel group, non inferiority study. Methods: Patients (n=205) with mild to moderate asthma continuing on the lowest dose of inhaled corticosteroid were recruited from 3 different centers across India. Patients were randomly assigned to receive either seratrodast 80 mg (n=103) or montelukast 10 mg (n=102) once daily for 28 days. The treatments were compared for improvement from the baseline values, as per the changes in asthma symptom score (wheezing, shortness of breath, expectoration, cough and chest tightness), lung function parameters (PEF, FVC and FEV1), sputum and mucociliary parameters [fucose, eosinophil cationic protein (ECP) and albumin]. Results: Seratrodast and montelukast showed improvement in the clinical parameters of asthma as well as in the lung function tests and sputum parameters from baseline. Both the treatments significantly increased mean values of PEF, FVC and FEV1 from the baseline after a 4 week treatment but seratrodast produced significantly greater improvement in PEF (0.416 L/s, P=.01). Moreover, there was significantly more reduction in expectoration score (P=.01), sputum concentrations of ECP (P<.001) and albumin (P<.001) in seratrodast group, signifying improvement in asthma condition. The two treatment groups had similar tolerability profiles. Mild increase in hepatic enzymes was seen in both the groups with no clinical significance. No serious adverse events were observed during the study. Conclusions: Seratrodast, a Thromboxane A2 receptor antagonist, was found to be better in the improvement of PEF, reduction in expectoration, ECP and albumin levels as compared to montelukast. Seratrodast can be recommended as a controller medication in mild to moderate asthma.

Thromboxane A2 receptor induces proliferation of rheumatoid arthritis synovial cells by up-regulation of cyclooxygenase-2 / 中国病理生理杂志

AIM:To examine the effects of thromboxane A 2 receptor ( TXA2 R) , the downstream product of cy-clooxygenase-2 (COX-2), on the proliferative ability and COX-2 expression in rheumatoid arthritis (RA) synovial cells. METHODS:The effects of TXA2 R antagonist SQ29548 and agonist U46619 on the proliferation of RA synovial cell line MH7A were detected by MTS cell proliferation assay , and their effects on COX-2 mRNA expression in MH7A cells were al-so examined by real-time PCR.In addition, the possible effect of U46619 on the proliferation of MH7A cells, when COX-2 was knocked down by siRNA , was determined by BrdU cell proliferation assay .RESULTS:SQ29548 inhibited the cell proliferation and the mRNA level of COX-2 while U46619 enhanced them.Moreover, U46619 reconstitute the proliferative ability of MH7A cells to some extent that inhibited by COX-2 siRNA.CONCLUSION: In RA synovial cells, TXA2R is able to control COX-2 expression, while it also mediates the effects of COX-2, suggesting that TXA2R might be an ideal candidate for RA treatment .

A study on correlation between thromboxane A2 receptor gene polymorphism and aspirin resistance / 中国中西医结合急救杂志

Objective To investigate the association between thromboxane A2 receptor(TXA2R)gene C795T, T924C,G1686A,rs2271875,rs768963 polymorphisms and aspirin resistance(AR)in Chinese Han population. Methods 168 in-patients with cerebral infarction who had been given aspirin from Zhejiang Provincial Taizhou Central Hospital from October 2009 to May 2013 were enrolled. The platelet aggregation rate was conducted by optical method. The inspections of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C)were conducted by enzymatic colorimetry,whereas blood glucose was tested by hexokinase method. The genotypes of three exons loci C795T,T924C,G1686A and two promoters loci rs2271875,rs768963 polymorphisms in TXA2R gene were detected by the polymerase chain reaction-ligase detection reaction(PCR-LDR)technique. The patients were divided into aspirin sensitive group(AS group,139 cases) and AR group(39 cases)according to the aspirin sensitive degree. The differences between two groups in age, smoking,serum TG,TC,HDL-C,LDL-C,concentration of blood glucose and blood pressure(systolic pressure, diastolic pressure)were compared,and in the mean time,the differences between two groups of TXA2R C795T, T924C,G1686A,rs2271875,rs768963 genotype distribution were also compared. Results AR group had higher incidences of cigarette smoking〔89.7%(35/39)vs. 69.8%(90/129)〕and high blood sugar(mmol/L:8.086±2.785 vs 5.631±1.662,P0.05). It was shown that there was no correlation between TXA2R gene polymorphism and AR. Conclusion The patients with smoking,high concentration of blood glucose have a higher incidence of AR,no correlation between TXA2R gene polymorphism and AR is found.

Association of thromboxane A2 receptor gene polymorphism with wheezing episode after RSV infection in children / 中国综合临床

Objective To investigate the potential role of respiratory syncytial virus (RSV) in wheezing episode in children, and to assess the association of the thromboxane A2 receptor gene (TBXA2R) T924C polymorphism with wheezing after RSV infection. Methods From may to december in 2008, one hundred and twenty-five asthmatic children who were suffering from acute episode were recruited as cases and 49 healthy children as controls in our Polymerase chain reactions-Restriction fragment length polymorphism (PCR-RELP) techniques were used to detect the TBXA2R SNP. RSV IgM and IgG were measured by ELISA. Results RSV specific antibody was positive in 57 asthmatic patients (45.6% ,57/125) and 8 controls (16.33% ,8/49) ,with significant difference between the two groups ( χ2 = 12. 890, P = 0. age asthmatic group and 76. 92% (30/39) in the <3 years of age asthmatic group, with significant difference between the two groups (χ2 = 22. 420, P = 0. 000 ). The genotypes distribution in the asthmatic patients was significantly different from that in the controls(χ2 = 5. 346, P = 0. 021). The frequency of TC and CC genotypes in the cases was significantly higher than that in the control group. The allele frequencies of T and C allele were similar in the two groups ( χ2 =2.660, P=0.103). Conclusions RSV infection was one of the factors that associated with asthma acute episode, especially in children younger than 3 years. The TC,CC genotypes increase the chance of wheezing in children infected by RSV.