Inhibition of T cell cAMP formation by cyclosporin A and FK506.
The influence of the immunosuppressants, cyclosporin A (CsA) and FK506, on cAMP formation was studied in T cells from healthy controls and patients with psoriasis. While basal cAMP levels were not affected, CsA (1 microM) and FK506 (2 nM) prevented the isoprenaline (0.1 microM)-induced increase in cAMP formation. Half-maximal inhibition by FK506 and CsA was observed at about 0.2 nM and 20 nM, respectively. In addition, both agents significantly reduced (by about 50%) the forskolin (8 microM)-stimulated cAMP formation. No differences were noted in cAMP responses (basal, stimulation by isoprenaline, inhibition by CsA and FK506) of T cells from healthy controls and psoriatic patients. We conclude that CsA and FK506 potently and efficiently interfere with the stimulatory adenylyl cyclase pathway in T cells and that regulation of T cell cAMP formation is apparently not altered in psoriasis.
Ockenfels
H M
HM
Hautklinik, Universitätsklinikum Essen, Germany.
Wagner
S N
SN
Oeljeklaus
P
P
Schneck
B
B
Nussbaum
G
G
Jakobs
K H
KH
Goos
M
M
D000328:Adult; D000368:Aged; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D005576:Colforsin; D016572:Cyclosporine; D000242:Cyclic AMP; D007545:Isoproterenol; D016559:Tacrolimus