Reversible inhibition of keratinocyte thymidine incorporation by the calmodulin antagonist, W-7.
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.
Hirokawa
M
M
Department of Dermatology, Asahikawa Medical College, Japan.
Hashimoto
Y
Y
Ohkuma
N
N
Mizumoto
T
T
Iizuka
H
H
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*
D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D013482:Superoxide Dismutase; D000262:Adenylyl Cyclases; D013936:Thymidine