Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils.

Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils. Research Abstract Details 

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Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils. Abstract Text:

Chantal Cossette,Sinead E Walsh,Seongjin Kim,Gue-Jae Lee,John A Lawson,Sophie Bellone,Joshua Rokach,William S Powell,

Prostaglandin (PG) D2 acts through both the DP(1) receptor, which is coupled to adenylyl cyclase, and the DP2 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 DP2 agonist so far reported is 15R-methyl-PGD2, in which the hydroxyl group has the unnatural R configuration. In contrast, the corresponding analog possessing the natural 15S configuration is approximately 75 times less potent. This raised the question of whether the isoprostane 15R-PGD2 might have potent DP2 receptor-mediated biological activity. We therefore chemically synthesized 15R-PGD2 and investigated its biological activity. This compound elicited DP2 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 PGD2. In contrast, it had only a weak effect on DP1 receptor-mediated adenylyl cyclase activity in human platelets. We also investigated the effects of modification of the 9-hydroxyl and 11-oxo groups of PGD2. Both PGK2, in which the 9-hydroxyl group is replaced by an oxo group, and 11-deoxy-11-methylene PGD2, in which the 11-oxo group is replaced by a CH2 group, have little or no DP1 or DP2 agonist activity. However, the 11-methylene analog is a DP2 antagonist (IC50, approximately 2 microM). We conclude that 15R-PGD2, which may be generated by oxidative stress, is a potent and selective DP2 agonist and that modification of the 11-oxo group of PGD2 can result in DP2 antagonist activity.

Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils. Publishing Authors By Initials

C Cossette,SE Walsh,S Kim,GJ Lee,JA Lawson,S Bellone,J Rokach,WS Powell,

For similar natural sciences: chemistry: chemistry, organic: isomerism: stereoisomerism research abstracts see: natural sciences: chemistry: chemistry, organic: isomerism: stereoisomerism research

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Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of pharmacology and experimental thera

VOLUME: 320

Page Numbers: 173-9

Journal Abbreviation: J. Pharmacol. Exp. Ther.

ISSN: 0022-3565

DAY: 13

MONTH: 10

YEAR: 2006

Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376362

Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils. Keywords Mesh Terms:

KEYWORDS: Stereoisomerism

MESH TERMS: drug effects

Chemical & Substance for Abstract: Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils. Information

Substance Name: 15-methylprostaglandin D2

Registry Number: 85280-90-6

Grant and Affiliation Information for Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2 on human eosinophils and basophils.

AFFILIATION: Meakins-Christie Laboratories, Department of Medicine, McGill University, 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada.

Country: United States

AGENCY: United States NHLBI

GRANT: HL81873

ACRONYM: HL

MEDLINETA: J Pharmacol Exp Ther

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