[Effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase isozyme type III/IV inhibitor, on the release of histamine from human peripheral leukocytes].
We studied the effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase (PDE) isozyme type III/IV inhibitor, and salbutamol on the release of histamine from activated human peripheral leukocytes. We stimulated the leukocyte suspensions with calcium ionophore A23187 (Ca-I, 10(-6 M) accompanied with SDZ ISQ 844 (10(-7) M, 10(-6) M, 10(-5) M), salbutamol (10(-7) M, 10(-6) M, 10(-5) M) and combination of SDZ ISQ 844 and salbutamol (10(-7) M, 10(-6) M, 10(-5) M), and measured the levels of histamine in the supernatant fluid and total cyclic AMP levels in the leukocyte suspensions. The increase of histamine levels induced by Ca-I was significantly inhibited by SDZ ISQ 844 (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). Salbutamol at the concentration until 10(-5) M did not inhibit the increase of histamine levels. Combination of SDZ ISQ 844 and salbutamol significantly inhibited the increase of histamine levels (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). The inhibition of the histamine release by SDZ ISQ 844 (10(-5) M was enhanced significantly by salbutamol (10(-5) M) (p < 0.05). Total cyclic AMP levels in the leukocytes suspensions increased significantly by SDZ ISQ 844 (10(-5) M) and combination of SDZ ISQ 844 and salbutamol (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). The increase of cyclic AMP levels by SDZ ISQ 844 (10(-5) M) was enhanced by salbutamol significantly (p < 0.01). These results suggest that selective inhibition of PDE isozyme type III/IV protects the release of histamine from human activated leukocytes in connection with intracellular cyclic AMP levels and the protection is enhanced by beta-agonist.
Horikoshi
S
S
First Department of Internal Medicine, School of Medicine, Showa University.
Imai
T
T
Okamoto
M
M
Sugeta
A
A
Idaira
K
K
Adachi
M
M
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism*; D010208:Papaverine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; C088309:SDZ ISQ 844; D010208:Papaverine; D000242:Cyclic AMP; D000420:Albuterol