Effect of 1,25-dihydroxyvitamin D3 on adenylate cyclase and protein kinase C in pig epidermis.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is suggested to be involved in the regulation of keratinocyte proliferation and differentiation. Recent evidence also indicates its potential value for the treatment of psoriasis, where the alteration of various transmembrane signalling systems has been well documented. Using porcine epidermis, we investigated the effect of 1,25(OH)2D3 on adenylate cyclase and protein kinase C systems, both of which are markedly altered in the psoriatic hyperproliferative epidermis. The effect was compared with that of another anti-psoriatic agent, hydrocortisone. Neither 1,25(OH)2D3 nor hydrocortisone revealed any effect on cyclic AMP levels or adenylate cyclase responses of epidermis. Long-term (24 h) hydrocortisone treatment, however, resulted in increased beta-adrenergic-, and prostaglandin E-adenylate cyclase responses. 1,25(OH)2D3-treatment had no effect on the epidermal adenylate cyclase responses following 24 h of incubation. The addition of both 1,25(OH)2D3 and hydrocortisone to the incubation medium resulted in the attenuation of the hydrocortisone-induced beta-adrenergic-, and prostaglandin E-adenylate cyclase responses of the epidermis. Neither agent had any effect on the cholera toxin-induced and forskolin-induced cyclic AMP accumulations of the epidermis. Neither 1,25(OH)2D3 nor hydrocortisone had any effect on the epidermal protein kinase C activity. It has been suggested that various anti-psoriatic agents might reveal their effect through the modulation of the adenylate cyclase system. Since 1,25(OH)2D3 had no effect when it was added singly to the incubation medium and rather inhibited hydrocortisone-induced adenylate cyclase stimulation, it is suggested that 1,25(OH)2D3 reveals its therapeutic efficacy through the mechanism, probably independently of the adenylate cyclase system.
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
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Koizumi
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Yasui
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Ohkawara
D000262:Adenylyl Cyclases / Q000032:analysis* / Q000187:drug effects; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology* / Q000502:physiology; D002455:Cell Division; D000242:Cyclic AMP / Q000032:analysis; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology*; D006854:Hydrocortisone / Q000494:pharmacology; D015603:Keratinocytes; D011493:Protein Kinase C / Q000032:analysis* / Q000187:drug effects; D011565:Psoriasis / Q000378:metabolism; D011863:Radioimmunoassay; D013552:Swine; D013997:Time Factors
D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D002117:Calcitriol; D006854:Hydrocortisone