INFLAMMATORY EFFECTS OF PROSTAGLANDIN D₂ IN RAT AND HUMAN SKIN

Abstract

I Intradermal injection of prostaglandin (PG) D1 and D2 in the human forearm produced a longlasting dose-related erythema. When compared with prostaglandin E1 or E2 the order of potency for erythema production was PGE1 > PGE2 > PGD2 > PGD1. 2 In rat skin, prostaglandin D2 but not D1 caused an increase in vascular permeability as quantitated by the Evans blue method and the 251I-albumin extravasation technique. Prostaglandin E2 was 3-5 times more potent than prostaglandin D2. 3 Prostaglandin D2 (10 ng) potentiated the increase in vascular permeability in rat skin produced by histamine, but not that produced by bradykinin. 4 Prostaglandin D2 (10, 20 and 50 ng) did not elicit oedema or hyperalgesia in the rat paw oedema test, but potentiated carrageenan-induced oedema; hyperalgesia was potentiated by doses of 100 ng and above.

The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions

“…Injection of PGD2 into human skin causes a longlasting erythema and an increase in blood flow but relatively little oedema (Flower et al, 1976;Soter et al, 1983;Maurice et al, 1987). Although PGD2 potentiates the increase in vascular permeability due to histamine in rat skin (Flower et al, 1976) there is no evidence for the potentiation of the wheal (Barnes & Heavey, 1986) erythema, or increased blood flow (Maurice et al, 1987) due to histamine injection in human skin.…”

“…Although PGD2 potentiates the increase in vascular permeability due to histamine in rat skin (Flower et al, 1976) there is no evidence for the potentiation of the wheal (Barnes & Heavey, 1986) erythema, or increased blood flow (Maurice et al, 1987) due to histamine injection in human skin. The relative proportions of histamine and PGD2 found in this study are similar to the ratio in blood draining whealed skin in immediate cold and heat urticaria (Heavey et al, 1986a;Koro et al, 1986) and we conclude that PGD2 has at best a minor role in immediate allergic reactions in skin.…”

“…Intradermal injection of PGD2 in the rat causes increased vascular permeability and in man produces a dose-related erythema (Flower et al, 1976;Maurice et al, 1987). Intravenous infusion causes vasodilatation .…”

Different responsiveness of prostaglandin D2‐sensitive systems to prostaglandin D2 and its analogues

“…Various actions ofthis prostaglandin have been reported, which include the anti-aggregatory activity on platelets of several species (Whittle et al, 1978), the contraction of airway smooth muscle (Hamberg et al, 1975;Schneider & Drazen, 1980), inflammatory effects (Flower et al, 1976;Soter et al, 1983), and the action on mast cells (Holgate et al, 1980). PGD2 also induces either contractions or relaxations in several vascular and gastrointestinal smooth muscle preparations (Horton & Jones, 1974;Whittle et al, 1979;Toda, 1982a).…”

Time course changes in levels of arachidonic acid and prostaglandins D2, E2, F2 alpha in human skin following ultraviolet B irradiation.

“…erythema to arachidonic acid and its prePresent address: *Centre International de Recherches Dermatologique, Sophia Antipolis, 06560 Valbonne, France. 0306-5251/80/050453-05 $01.00 viously measured metabolites, it is possible that other vasoactive metabolites of arachidonic acid may be also involved. Since skin homogenates form prostaglandjn D (Nugteren & Hazelhof, 1973), and intradermally injected prostaglandin D2 (PGD2) produced a long-lasting dose-related erythema in human skin and potentiates the increased vascular permeability due to histamine (Flower, Harvey & Kingston, 1976) 6,8,9,11,12,14,15 octadeutero arachidonic acid (d8 arachidonic acid) in 1.0 ml of 15O/M indomethacin in 95% aqueous ethanol. Where possible samples were immediately extracted; if not, they were stored at -20°C prior to extraction.…”