title: Reversible inhibition of keratinocyte thymidine incorporation by the calmodulin antagonist, W-7.
abstract: Although calmodulin has been suggested as an important regulator of keratinocyte proliferation, its precise role remains unknown. We employed a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), to examine the role of calmodulin on keratinocyte proliferation. N-(6 aminohexyl-1-naphthalenesulfonamide (W-5), a chlorine-deficient analogue of W-7 with little anti-calmodulin activity, was used as the control. W-7 markedly inhibited thymidine incorporation of pig epidermis at concentrations close to its anti-calmodulin activity; W-5 had no effect on the thymidine incorporation. The inhibitory effect of W-7 was reversible; the removal of W-7 from the incubation medium resulted in the reinitiation of the thymidine incorporation, suggesting that W-7 is not a cytotoxic agent. These results are consistent with the view that calmodulin is an essential regulator of keratinocyte proliferation. The epidermal beta-adrenergic response, which is decreased in various hyperproliferative epidermal abnormalities, was increased in W-7-treated hypoproliferative epidermis. The epidermal SOD activity, which is also decreased in the hyperproliferative epidermis, however, was not affected by the W-7 treatment.
authors.affiliation: Department of Dermatology, Asahikawa Medical College, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirokawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: N
authors.initials: N
authors.lastname: Ohkuma
authors.forename: T
authors.initials: T
authors.lastname: Mizumoto
authors.forename: H
authors.initials: H
authors.lastname: Iizuka
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000502:physiology; D002455:Cell Division; D004817:Epidermis / Q000201:enzymology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013552:Swine; D013936:Thymidine / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D013482:Superoxide Dismutase; D000262:Adenylyl Cyclases; D013936:Thymidine