Biomaterial Database

Effects of two novel inhibitors of 5-lipoxygenase, L-651,392 and L-651,896, in a guinea-pig model of epidermal hyperproliferation. 1987

C C Chan, and L Dubois, and V Young

Department of Pharmacology, Merck Frosst Canada, Pointe Claire-Dorval, Quebec.

The effects of two novel and structurally different 5-lipoxygenase inhibitors, L-651,392 (4-bromo-2,7-dimethoxy-3H-phenothiazin-3-one) and L-651,896 (2,3-dihydro-6-(3-(2-hydroxymethyl)phenyl-2-propenyl)-5-benzo furanol), on epidermal proliferation were examined in the guinea-pig ear stimulated with the calcium ionophore A23187. Topical application of A23187 on the guinea-pig ear induced epidermal hyperproliferation which could be quantitated by tritiated-thymidine incorporation into DNA in the heat-separated epidermis. The ionophore-induced response was inhibited dose dependently by either L-651,392 or L-651,896 when the guinea-pigs were pretreated topically with these compounds. In separate experiments, it was demonstrated that A23187 induced a significant increase in the levels of immunoreactive-LTB4 in the guinea-pig ear which could be blocked by either inhibitors. It was suggested that L-651,392 and L-651,896 inhibited the ionophore-induced epidermal proliferation via their inhibitory action on the 5-lipoxygenase pathway of arachidonic acid metabolism.

UI	MeSH Term	Description	Entries
D007975	Leukotriene B4	The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)	5,12-HETE,5,12-diHETE,LTB4,Leukotriene B,Leukotriene B-4,Leukotrienes B,5,12 HETE,5,12 diHETE,B-4, Leukotriene,Leukotriene B 4
D008297	Male		Males
D010640	Phenothiazines	Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.
D011458	Prostaglandins E	(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.	PGE
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005260	Female		Females
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000001	Calcimycin	An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.	4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-((3,9,11-trimethyl-8-(1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl)-1,7-dioxaspiro(5.5)undec-2-yl)methyl)-, (6S-(6alpha(2S,3S),8beta(R*),9beta,11alpha))-,A-23187,A23187,Antibiotic A23187,A 23187,A23187, Antibiotic
D000078404	Epidermal Cells	Cells from the outermost, non-vascular layer (EPIDERMIS) of the skin.	Epidermal Cell,Epidermic Cells,Cell, Epidermal,Cell, Epidermic,Cells, Epidermic,Epidermic Cell