The identification of phorbolol myristate acetate as a new metabolite of phorbol myristate acetate in mouse skin.
Aspects of the metabolism of phorbol myristate acetate (PMA) in mouse skin were investigated. Phorbolol myristate acetate (PHMA), a potential metabolite of PMA in mouse skin, was prepared from PMA by NaBH4 reduction of the C-5 carbonyl group of PMA to a secondary alcohol. The structure of PHMA was assigned on the basis of spectral and chemical evidence. PHMA had an inflammatory effect in mouse skin equal to or slightly less than PMA, on the basis of the dermal infiltration of lymphocytes and neutrophils and interfollicular epidermal hyperplasia. Application of PHMA and PMA to mouse skin resulted in equal increases in numbers of interfollicular epidermal basal layer mitotic cells after 28 hr. PHMA was found to be nearly as effective as PMA in increasing the incorporation of [3H]thymidine into interfollicular epidermal basal layer cells after 28 hr. When tritiated PMA was applied to mouse skin, PHMA was identified as a metabolite. PHMA was present in about 1.7% of the amount of PMA. When tritiated PHMA was applied to mouse skin, PMA was not detected as a metabolite in the mouse skin extracts.
D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008938:Mitosis / Q000187:drug effects; D010704:Phorbols / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine