8-Epi-PGF2 alpha, a novel noncyclooxygenase-derived prostaglandin, constricts airways in vitro

Autor: Ivana Kawikova, Magdi H. Yacoub, Peter J. Barnes, Samad Tadjkarimi, Tsuneyuki Takahashi, Maria G. Belvisi
Rok vydání: 1996
Předmět:
Adult
Male
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Contraction (grammar)
Adolescent
Prostaglandin Antagonists
Bronchoconstriction
Xanthones
Guinea Pigs
Receptors
Prostaglandin
Prostaglandin
In Vitro Techniques
Dinoprost
Critical Care and Intensive Care Medicine
Dioxanes
Thromboxane A2
chemistry.chemical_compound
Internal medicine
Animals
Humans
Medicine
Receptor
F2-Isoprostanes
Dose-Response Relationship
Drug
biology
business.industry
Prostanoid
Middle Aged
respiratory system
Prostaglandin antagonist
musculoskeletal system
Prostaglandin Endoperoxides
Synthetic
Trachea
Endocrinology
Xanthenes
chemistry
15-Hydroxy-11 alpha
9 alpha-(epoxymethano)prosta-5
13-dienoic Acid
cardiovascular system
biology.protein
Female
lipids (amino acids
peptides
and proteins)
Cyclooxygenase
medicine.symptom
business
Muscle Contraction
circulatory and respiratory physiology
Muscle contraction
Zdroj: American Journal of Respiratory and Critical Care Medicine. 153:590-596
ISSN: 1535-4970
1073-449X
DOI: 10.1164/ajrccm.153.2.8564103
Popis: 8-Epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) is an F2-isoprostane formed via a noncyclooxygenase pathway. We investigated whether 8-epi-PGF2 alpha has any effects on isolated guinea-pig and human airway smooth-muscle tone, and characterized the receptor involved in these effects. Cumulative concentration responses to 8-epi-PGF2 alpha in the absence or presence of prostanoid TP- and EP1-receptors antagonists (ICI 192, 605 and AH 6809, respectively) were compared with the responses to U46619 (a thromboxane A2 mimetic) and PGF2 alpha. 8-epi-PGF2 alpha contracted airway smooth muscle with a rank order of potency of U46619 > PGF alpha > 8-epi-PGF2 alpha for guinea pig and U46619 > 8-epi-PGF2 alpha > PGF2 alpha for human smooth muscle. ICI 192,605 inhibited guinea-pig tracheal contraction produced by U46619 (pA2 = 10.0) with a similar potency to its inhibition of the contraction induced by 8-epi-PGF2 alpha (apparent pKB = 10.2, 10.3), but not that induced by PGF2 alpha (apparent pKB = 6.6). AH 6809 inhibited contraction induced by PGF2 alpha (pA2 = 6.6) with a greater potency than contraction induced by U46619 (apparent pKB = 5.1, 5.2) or 8-epi-PGF2 alpha (apparent pKB = 5.3). In human airways, ICI 192,605 inhibited contraction induced by U46619 and 8-epi-PGF2 alpha with apparent pKB values of 9.5 and 9.4, respectively, and AH 6809 inhibited contraction induced by 8-epi-PGF2 alpha with apparent pKB values of 5.7 and 5.4. We conclude that 8-epi-PGF2 alpha contracts human and guinea-pig airways via prostanoid TP receptors. However, if 8-epi-PGF2 alpha is formed in asthma, its production, unlike that of other prostanoids, would not be inhibited by cyclooxygenase inhibitors.
Databáze: OpenAIRE
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