[The experimental study of the effect of cyclosporin A on epidermis].
The direct effects of immunosuppressive agent; cyclosporin A (CsA) on epidermal cells were examined by using three different kinds of systems; a pig skin explant culture system, receptor-adenylate cyclase-cyclic AMP and cyclic AMP phosphodiesterase system and DNA synthesis system. CsA inhibited epidermal outgrowth at concentrations of 12 micrograms/ml and 20 micrograms/ml. But neither epidermal outgrowth nor mitoses was inhibited by CsA up to the concentration of 6 micrograms/ml. Therapeutic serum levels of CsA(100-400 ng/ml)augmented epinephrine-adenylate cyclase-cyclic AMP response of pig epidermis, but prostaglandin E1-, adenosine- or histamine-adenylate cyclase cyclic AMP responses were not affected significantly. Both low Km and high Km cyclic AMP phosphodiesterase activities were not altered by CsA. Thymidine incorporation of pig epidermis was markedly inhibited in the keratome sliced hyperproliferative epidermis taken 48 hours after 60 times tape stripping even with short time incubation by the therapeutic serum level of CsA(200 ng/ml), although even 10 times serum level of CsA did not show any inhibitory effect on thymidine incorporation in the untreated normal pig epidermis with short time incubation.
Kato
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N
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D007633:Keratins; D013552:Swine
D003524:Cyclosporins; D007633:Keratins; D004247:DNA; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases