Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce serum colestrol levels induces intense flushing in humans. We have recently shown that the vasodilation following ingestion of niacin is due to the release of prostaglandin (PG) D₂. However, the site from which PGD₂ is released is not known. It has previously been shown that topical application of methylnicotinate causes local cutaneous erythema. Thus, we investigated whether topical methylnicotinate causes a release of PGD₂ locally from skin and the possibility that skin may be a major contributor to the release of PGD₂ when niacin is administered by mouth.

Topical administration of methylnicotinate (10^-1 M) to the forearms of human volunteers resulted in 58- to 122- times increases in levels of the PGD₂ and 9α,11β-PGF₂ were not found in blood drawn simultaneously from veins in the contralateral arm, indicating that the PGD₂ was released from the site of methylnicotinate application. The release of PGD₂ in response to topically applied methylnicotinate occurred in a dose-dependent manner over the concentration range of 10^-3 to 10^-1 M. The release of PGD₂ was not accompanied by a release of histamine, suggesting that the release of PGD₂ was not from the mast cell. Following oral ingestion niacin, levels of PGD₂ in superficial venous blood draining the skin were 14 to 1200 times higher than the level in arterial blood supplying the skin is a major site from which PGD₂ is released following oral ingestion of niacin.

These studies thus indicate that the cutaneous vasodilation that occurs following oral administration of niacin is primarily due to a release of PGD₂ from a niacin responsive cell that resides in the skin.