Calmodulin inhibition by anthralin? Investigations in vitro and in vivo.
Increased epidermal calmodulin (CaM) levels have been reported in psoriatic lesions. It has been suggested that CaM inhibition might be of relevance in the treatment of psoriasis vulgaris. Therefore we investigated the possible CaM inhibition by the antipsoriatic drug anthralin in vitro and in vivo. For in vitro studies, anthralin (0.44 mM) effects on the CaM-dependent Ca++-ATPase of CaM-depleted erythrocyte ghosts were assessed. At 100 microM Ca++, no enzyme inhibition was measured either in the presence or absence of CaM. At 2 microM Ca++ anthralin inhibited the CaM stimulation of membrane-bound ATPase for 50% in presence of CaM. For in vivo studies, skin biopsies were taken from anthralin-treated psoriatic lesions without scaling but still palpable infiltration during the first 3 weeks of therapy. Lesions with anthralin-induced irritation were excluded. The epidermal CaM level was determined by measuring the ability of soluble epidermal protein to activate the Ca++-ATPase in CaM-depleted erythrocyte ghosts. Epidermal CaM was 7.07 +/- 4.57 (mean +/- SD) microgram CaM/mg soluble epidermal protein. This is a 6-fold increase compared to normal human epidermis and a 3-fold increase compared to nontreated lesional psoriatic epidermis (p less than 0.01 and 0.02, respectively). The results argue against CaM inhibition of psoriatic epidermal keratinocytes as the primary event in the antipsoriatic action of anthralin.
Wollina
U
U
Clinic and Policlinic of Dermatology, Friedrich Schiller University, Jena, GDR.
Klinger
R
R
Wetzker
R
R
Knopf
B
B
D000875:Anthralin / Q000494:pharmacology* / Q000627:therapeutic use; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004817:Epidermis / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D011565:Psoriasis / Q000188:drug therapy / Q000473:pathology
D002147:Calmodulin; D000252:Calcium-Transporting ATPases; D000875:Anthralin