Binding characteristics of the new thromboxane A2/prostaglandin H2 receptor antagonist [3H]BAY U 3405 to washed human platelets and platelet membranes

Theis, Jochen G.W.; Dellweg, Hansgeorg; Perzborn, Elisabeth; Gross, R

doi:10.1016/0006-2952(92)90441-k

Cited by 22 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ramatroban is a drug having specific high affinity binding site of human platelets and platelet membranes that represents the TXA 2 receptor [19]. In nasal allergy, Narita et al [20] and Kayasuga et al [18] also showed that ramatroban significantly inhibited nasal rubbing and sneezing induced by antigen in guinea pigs and mice.…”

Section: Discussionmentioning

confidence: 97%

A chronic model for evaluating the itching associated with allergic conjunctivitis in rats

Minami

Kamei

2004

International Immunopharmacology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

A chronic model for evaluating the itching associated with allergic conjunctivitis in rats

Minami

Kamei

2004

International Immunopharmacology

View full text Add to dashboard Cite

“…The receptor specificity of the effects of U46619 and thrombin was tested by using the selective TXA2 receptor antagonist Bay U 3405 (29) as well as the thrombin receptor peptide SFLLRN-NH2. This thrombin receptor peptide represents the new N terminus of the proteolytically activated thrombin receptor (13) and is sufficient to activate human platelets (30).…”

Section: Methodsmentioning

confidence: 99%

G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets.

Offermanns

Laugwitz

Spicher

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

412

289

View full text Add to dashboard Cite

Using subtype-specific antisera, we were able to identify the recently described alpha subunits of G12 and G13 in platelet membranes as 43-kDa proteins. Activation of the thromboxane A2 and the thrombin receptors in platelet membranes led to increased incorporation of the photoreactive GTP analogue [alpha-32P]GTP azidoanilide into immunoprecipitated alpha 12 and alpha 13, indicating that both receptors couple to G12 and G13. In addition, both activated receptors were demonstrated to couple to one or more members of the Gq family. In the absence of receptor agonists, incorporation of [alpha-32P]GTP azidoanilide into alpha 12 and alpha 13 was low over a long time period (up to 45 min) due to an obviously low basal nucleotide exchange rate, whereas an agonist-stimulated photolabeling of alpha 12 and alpha 13 could be observed after 4-8 min and reached a maximum after 30-45 min. Effective activation of G12 and G13 via the thromboxane A2 and the thrombin receptors was not dependent on the presence of GDP. Our results provide evidence that G12 and G13 play a functional role in transmembrane signal transduction and suggest that both proteins are involved in pathways leading to platelet activation.

show abstract

“…The finding that indomethacin, in addition to its potent cyclooxygenase inhibitory activity, is also a DP 2 receptor agonist (Hirai et al, 2002) led to a search for other indolic compounds that might have antagonist activity. The first DP 2 antagonist to be identified was ramatroban (IC 50 approximately 100 nM) (Sugimoto et al, 2003), which is an indolic compound that was originally developed by Bayer as a selective TP receptor antagonist (Theis et al, 1992). Minor structural modification of ramatroban resulted in a highly selective and potent DP 2 antagonist (Ulven and Kostenis, 2005).…”

Section: Effects Of 15r-pgdmentioning

confidence: 99%

Agonist and Antagonist Effects of 15 R-Prostaglandin (PG) D2 and 11-Methylene-PGD2 on Human Eosinophils and Basophils

Cossette

Walsh²,

Kim³

et al. 2007

The Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

Prostaglandin (PG) D 2 acts through both the DP 1 receptor, which is coupled to adenylyl cyclase, and the DP 2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells), which is present on eosinophils, basophils, and Th2 cells and results in cell activation and migration. The most potent prostanoid DP 2 agonist so far reported is 15R-methyl-PGD 2 , in which the hydroxyl group has the unnatural R configuration. In contrast, the corresponding analog possessing the natural 15S configuration is ϳ75 times less potent. This raised the question of whether the isoprostane 15R-PGD 2 might have potent DP 2 receptor-mediated biological activity. We therefore chemically synthesized 15R-PGD 2 and investigated its biological activity. This compound elicited DP 2 receptor-mediated CD11b expression in human basophils and eosinophils and induced actin polymerization and migration in eosinophils with a potency about the same as that of PGD 2 . In contrast, it had only a weak effect on DP 1 receptor-mediated adenylyl cyclase activity in human platelets. We also investigated the effects of modification of the 9-hydroxyl and 11-oxo groups of PGD 2 . Both PGK 2 , in which the 9-hydroxyl group is replaced by an oxo group, and 11-deoxy-11-methylene PGD 2 , in which the 11-oxo group is replaced by a CH 2 group, have little or no DP 1 or DP 2 agonist activity. However, the 11-methylene analog is a DP 2 antagonist (IC 50 , ϳ2 M). We conclude that 15R-PGD 2 , which may be generated by oxidative stress, is a potent and selective DP 2 agonist and that modification of the 11-oxo group of PGD 2 can result in DP 2 antagonist activity.

show abstract

Binding characteristics of the new thromboxane A2/prostaglandin H2 receptor antagonist [3H]BAY U 3405 to washed human platelets and platelet membranes

Cited by 22 publications

References 18 publications

A chronic model for evaluating the itching associated with allergic conjunctivitis in rats

A chronic model for evaluating the itching associated with allergic conjunctivitis in rats

G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets.

Agonist and Antagonist Effects of 15 R-Prostaglandin (PG) D2 and 11-Methylene-PGD2 on Human Eosinophils and Basophils

Contact Info

Product

Resources

About