Inhibition of IgE-mediated histamine release from human peripheral leukocytes by selective phosphodiesterase inhibitors.
Several phosphodiesterase (PDE) inhibitors with the capacity to inhibit the PDE IV isoenzyme produce dose-dependent inhibition of IgE-mediated histamine release (HR) from human peripheral leukocytes in vitro. Inhibition reached a maximum after 20 min of preincubation (IC30: 6-30 microM, IC50: 30-80 microM). Motapizone--a potent inhibitor of the isoenzyme PDE III--was much less effective, thus giving indirect evidence that PDE IV plays a predominant role in the control of cAMP cleavage in human basophils. The inhibiting effect of PDE-III/IV-selective compounds on IgE-mediated HR did not exceed the action of PDE-IV-selective inhibitors. The inhibition of anti-IgE-induced HR by zardaverine (a PDE-III/IV-inhibiting compound) was synergistically enhanced in the combined presence of forskolin or the recently synthesized histamine H2-agonist FRA 19).
Kleine-Tebbe
J
J
Dept. of Clin. Immunology and Asthma OPD, University Hospital Rudolf Virchow, Freie Universität Berlin, Germany.
Wicht
L
L
Gagné
H
H
Friese
A
A
Schunack
W
W
Schudt
C
C
Kunkel
G
G
D001491:Basophils / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D007073:Immunoglobulin E