Release of markedly increased quantities of prostaglandin D2 from the skin in vivo in humans following the application of sorbic acid.
METHODS
Sorbic acid is a preservative that can induce cutaneous vasodilation characterized by erythema, urticaria, and stinging when applied topically to humans. Previous studies have suggested that prostaglandins may mediate the vasodilation, but the prostaglandin responsible has not been established. Recently, we have shown that cutaneous erythema similar to that associated with the application of sorbic acid is induced by topical administration of methylnicotinate and is mediated by the release of prostaglandin D2 (PGD2) from the skin. Therefore, we examined whether the cutaneous vasodilation induced by sorbic acid is also mediated by this prostaglandin in humans.


RESULTS
Topical application of 1% sorbic acid to the forearms of four human volunteers resulted in 250- to 620-fold increases in levels of PGD2 and 15- to 58-fold increases in levels of the metabolite of PGD2, 9 alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated sites. There were no increases in the release of the other vasodilatory prostaglandins, PGE2 or prostacyclin (PGI2). The release of PGD2 in response to topically applied sorbic acid occurred in a dose-dependent manner and was not accompanied by a release of histamine, suggesting that the release of PGD2 was not from the mast cell.


CONCLUSIONS
The cutaneous vasodilation that occurs following the administration of sorbic acid is primarily due to a release of PGD2 from a cellular source in the skin.
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.
J D
JD
Morrow
T A
TA
Minton
J A
JA
Awad
L J
LJ
Roberts
D000287:Administration, Topical; D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000378:metabolism* / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000378:metabolism*; D013011:Sorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology
D015237:Dinoprost; D001241:Aspirin; D015230:Prostaglandin D2; D013011:Sorbic Acid