Anti-inflammatory effect of prostanoids in mouse and rat skin: evidence for a role of EP3-receptors.
The effects of prostaglandin E1 (PGE1) and certain PGE-analogs on edema formation were investigated in mouse and rat skin. In the mouse, intradermal administration of both zymosan-activated serum (ZAS) (5-50% per site) and platelet-activating factor (PAF) (0.1-5.0 nmol/site) caused dose-related increases in edema formation. PGE1 (0.003-3.0 nmol/site) caused a dose-related inhibition of the edema response to ZAS, whereas a dose of 0.3 nmol potentiated the edema response to PAF. Sulprostone, which is selective for EP1 and EP3 PGE-receptors, produced a potent inhibition of the edema responses to both ZAS (80%) and PAF (60%). Misoprostol, which is selective for both EP2- and EP3-receptors, inhibited the edema response to ZAS (> 40%) but had no effect on the response to PAF. Treatment of mice with the thromboxane A2-receptor antagonist GR32191B did not modify the anti-inflammatory activity of PGE1 or sulprostone. In the rat skin model, PGE1 produced only potentiation of the responses to both ZAS and PAF. However, sulprostone displayed significant inhibitory effects on the edema responses to both stimuli (40-50%). From these data we propose that the anti-inflammatory activity of PGE1 and of the two analogs sulprostone and misoprostol may be mediated via activation of the contractile EP3-receptor. Differences in the responses to prostanoids from one species to another may reflect differences in the relative densities of receptor subtypes mediating opposite effects.
Ahluwalia
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A
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, England.
Perretti
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D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001769:Blood; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004487:Edema / Q000209:etiology; D008297:Male; D051379:Mice; D016595:Misoprostol / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D015054:Zymosan / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010972:Platelet Activating Factor; D018078:Receptors, Prostaglandin E; D016595:Misoprostol; C016767:sulprostone; D015054:Zymosan; D000527:Alprostadil; D015232:Dinoprostone