Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce serum cholesterol 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 PGD2 and 25- to 33-times increases in levels of the metabolite of PGD2, 9 alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated sites. Increased levels of PGD2 and 9 alpha,11 beta-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 of 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 of the same arm. This finding indicates that 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.
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PMID:Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans. 137 50

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.
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PMID:Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. 247 89

The symptoms and hemodynamic alterations that accompany systemic mast cell activation have been attributed in large part to an excessive release of prostaglandin D2 (PGD2). Further, PGD2 has been implicated in the adverse effects of some pharmacologic agents (e.g. nicotinic acid). Quantitation of the major urinary metabolite of PGD2 has been invaluable in elucidating a role for PGD2 in these clinical entities and in the biochemical diagnosis of the disease systemic mastocytosis. However, the stable-isotope mass spectrometric assay originally developed for quantification of this metabolite has been too cumbersome for routine use. We now report improvements in the assay that greatly increase its utility by shortening sample processing and eliminating the need for purification using thin-layer chromatography. The precision and accuracy of the modified assay was evaluated and found to be comparable with the previously described assay. These modifications potentially allow wider use of the assay to explore the role of PGD2 in human disease and in the routine biochemical diagnosis of systemic mastocytosis and other disorders of mast cell activation.
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PMID:Simplification of the mass spectrometric assay for the major urinary metabolite of prostaglandin D2. 837 25

In rats and guinea-pigs both mast cell damage and histamine release in anaphylaxis were inhibited by pyridine, nicotinamide, diethylnicotinamide, nicotinic acid, isonicotinic acid and isonicotinic acid hydrazide, which are known to be inhibitors of diphosphopyridine nucleotidases. On the other hand these compounds potentiated histamine release and mast cell damage by compound 48/80 in guinea-pigs although inhibiting the same phenomena in rats. The relationship of these findings with the mechanism of histamine liberation in anaphylaxis is discussed.
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PMID:The inhibition of mast cell damage and histamine release in anaphylaxis by pyridine and diphosphopyridine nucleotidase inhibitors. Comparison with compound 48/80. 1377 70

Nicotinamide (niacinamide), a physiologically active form of niacin (nicotinic acid), in combination with zinc is being assessed in clinical studies for the treatment of inflammatory skin diseases such as acne vulgaris and bullous pemphigoid. The basis for these investigations is the variety of potential mechanisms of action of nicotinamide and zinc, including an anti-inflammatory effect via inhibition of leukocyte chemotaxis, lysosomal enzyme release, lymphocytic transformation, mast cell degranulation, bacteriostatic effect against Propionibacterium acnes, inhibition of vasoactive amines, preservation of intracellular coenzyme homeostasis, and decreased sebum production. Other possible mechanisms involve suppression of vascular permeability and inflammatory cell accumulation, as well as protection against DNA damage. The goal of this paper is to review the pathophysiology of inflammatory skin diseases and discuss the role, mechanisms of action, and safety of nicotinamide and zinc as therapeutic options for these disorders.
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PMID:The mechanisms of action of nicotinamide and zinc in inflammatory skin disease. 1687 73

Coronary artery disease is associated with increased serum levels of cholesterol, triglycerides and LDL, but low levels of HDL. The most potent agent capable of reversing this trend is the vitamin nicotinic acid (niacin). However, compliance even with extended-release preparations and addition of acetylsalicylic acid (ASA) is hampered by the development of a feeling of erythema and burning ("flush"), especially on the face. We recently showed that the natural flavonoids quercetin and luteolin can eliminate "flush", as well as inhibit both niacin-induced plasma prostaglandin D2 (PGD2) and serotonin increase in an animal model. We conducted a pilot clinical study in humans. Four normal male subjects received (a) 1 g immediate release niacin either alone or after (b) the dietary formulation (Algonot-plus) containing 150 mg quercetin per capsule. Subjects completed a visual scale (1 = no, 5 = worst response) symptom assessment. Erythema and burning sensation scores were both 4.75+/-0.50 and lasted for 3.63+/-1.11 hours. After Algonot-plus administration, both scores were reduced to 2.5+/-0.58 and lasted only for 1.68+/-0.70 hours. Quercetin also inhibited methylnicotinate-induced human mast cell PGD2 release. These preliminary results suggest that quercetin could reduce niacin-induced "flush" in humans.
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PMID:A quercetin containing supplement reduces niacin-induced flush in humans. 1883 18