Attenuation of ultraviolet radiation-induced edema and erythema with topical calmodulin and protein kinase C inhibitors.
We treated Skh:HR1 hairless albino mice, NSA mice and hairless albino guinea pigs topically with N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) or trifluoperazine (TFP) before or after ultraviolet (UV) irradiation. When applied before irradiation, W7 and TFP prevented edema in Skh-1 mice and W7 prevented UV-induced edema in NSA mice in a dose-dependent manner. Preirradiation treatment with 2% W7 reduced erythema in guinea pigs by 50%. Epidermal histology of UVR-treated Skh-1 mice pretreated with W7 before UVR was similar to unirradiated mice. W7 did not reverse or prevent these UV-induced effects when applied after irradiation. Neither TFP nor W7 absorbed UV based on forward scattering absorbance spectra; we conclude that neither are physical or chemical sunscreens. These results suggest that calmodulin and/or protein kinase C-dependent events are involved in manifesting some of the effects of UV irradiation on skin.
Anthony
F A
FA
Schering-Plough HealthCare Products, Inc., Memphis, TN 38151-0001, USA.
Dowdy
J C
JC
Costlow
M E
ME
D000042:Absorption; D000279:Administration, Cutaneous; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000473:pathology / Q000517:prevention & control*; D004890:Erythema / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006168:Guinea Pigs; D051379:Mice; D008812:Mice, Hairless; D008815:Mice, Inbred Strains; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012871:Skin Diseases / Q000473:pathology / Q000517:prevention & control*; D012885:Skinfold Thickness; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D013473:Sunscreening Agents / Q000627:therapeutic use; D014268:Trifluoperazine / Q000008:administration & dosage / Q000627:therapeutic use*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D002147:Calmodulin; D013449:Sulfonamides; D013473:Sunscreening Agents; D014268:Trifluoperazine; C017967:W 7; D011493:Protein Kinase C