UVB-induced calmodulin increase in pig epidermis: analysis of the effect of the calmodulin antagonist, W-13.

Calmodulin (CaM) is a multifunctional calcium-binding protein that has been implicated in the control of cell proliferation. In order to determine the role of CaM in keratinocyte proliferation, we investigated the effect of the CaM antagonist, W-13 on thymidine incorporation into pig epidermis. W-13 significantly inhibited thymidine incorporation into pig epidermis, while W-12, a closely related compound with much less anti-CaM activity, had little effect. The effect of W-13 was detected after as little as 2 h of incubation. Using a short-term (2-h) incubation system, the effects of other chemicals affecting various transmembrane signalling systems of keratinocytes were also investigated. None of these chemicals (epinephrine, histamine, forskolin, HA-1004, bradykinin, mezerein, phorbol 12-myristate, 13-acetate, H-7, staurosporin) inhibited thymidine incorporation. The effect of W-13 was reversible; its removal from the incubation medium resulted in the reinitiation of thymidine incorporation. Pig epidermis responded to 2.5 MED UVB irradiation showing an initial (24-48 h after irradiation) decrease and a subsequent (96-120 h after irradiation) increase in thymidine incorporation. The CaM content was not significantly altered during the initial hypoproliferative phase, but was significantly increased during the 72-120 h after UVB irradiation sometimes slightly preceding but mostly coinciding with the increase in thymidine incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)