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Cited by 76Eicosanoids and Hypertension PharmacologyAsthma and respiratory diseasesInflammatory mediators and NSAID effects

PGD2 metabolism in plasma: Kinetics and relationship with bioactivity on DP1 and CRTH2 receptors

Schuligoi, Rufina, Schmidt, Ronald, Geisslinger, Gerd, Kollroser, Manfred, Peskar, Bernhard A., Heinemann, Akos·2007·Biochemical Pharmacology
DOI 10.1016/j.bcp.2007.03.023
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Abstract

Prostaglandin (PG)D(2), an important mediator in allergic diseases, is rapidly transformed in plasma to active metabolites that bind and activate two distinct receptors, DP1 and CRTH2. Since the rate of PGD(2) degradation and the bioactivity of the resulting metabolites are still unclear, the aim of our study was to analyze the kinetics and biological effects of PGD(2) metabolites formed in plasma. Eosinophil shape change was taken as a parameter of chemotactic activation mediated by CRTH2 whereas inhibition of platelet aggregation served as a measure of DP1 activity. PGD(2) was degraded in plasma with an apparent half-life of approximately 30 min, accompanied by a loss of potency in inhibiting platelet aggregation as well as inducing eosinophil stimulation. Incubation of PGD(2) in plasma for 120 min caused an increase in the IC(50) for platelet aggregation by a factor of 6.5 and an increase of the EC(50) for eosinophil shape change by a factor of 7.2. However, tandem mass spectrometry analysis showed that incubation of PGD(2) in plasma for 120 min resulted in clearance of PGD(2) of more than 92%, which was mirrored by a continuous formation of Delta(12)-PGD(2) and Delta(12)-PGJ(2), whereas only small amounts of 15d-PGD(2) and 15d-PGJ(2) were detected. Interestingly, a rapid degradation of PGD(2) was also observed in serum, which was not prevented by pepsin digestion of serum preceding the addition of PGD(2). Therefore, despite extensive non-enzymatic metabolization of PGD(2) in plasma, its biological activity with respect to DP1 and CRTH2 is maintained through the formation of bioactive metabolites.

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  • Administration of granulocyte colony-stimulating factor reduced SWS amount and intensity at the beginning of the night and increased plasma levels of IL-1ra and soluble TNF receptors.

    “A reduction of SWS amount and intensity has been observed in the beginning of the night following administration of granulocyte colony-stimulating factor, which in parallel led to an increase of the plasma levels of endogenous antagonists of IL-1 and TNF, i.e., IL-1ra and soluble TNF receptors, respectively (497).”

    From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [497]

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Authors
Schuligoi, R., Schmidt, R., Geisslinger, G., Kollroser, M., Peskar, B. A., & Heinemann, A.
Affiliations
  • Medical University of Graz (AT)
  • Goethe University Frankfurt (DE)
Corresponding author
Schuligoi, Rufina
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2007-06
Volume
74
Issue
1
Pages
107-117
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2007.03.023
OpenAlex
W2089980371
Cited by
73
References
29
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 6
FWCI
2.57
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Austrian Science Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords
prostaglandin D2, plasma metabolism, DP1 receptor, platelet aggregation inhibition, chemotaxis, non-enzymatic degradation, allergic diseases
MeSH terms
Chemotactic Factors, Eosinophil, Chemotaxis, Collagen, Eosinophils, Humans, Kinetics, Leukocytes, Platelet Aggregation, Receptors, Immunologic, Receptors, Prostaglandin, Time Factors, Prostaglandin D2, Spectrometry, Mass, Electrospray Ionization, Cell Shape, Tandem Mass Spectrometry

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