Inhibitory effect of pemirolast, a novel antiallergic drug, on leukotriene C4 and granule protein release from human eosinophils.
To determine whether pemirolast, a new antiallergic drug, inhibits the activation of eosinophils, we investigated the effect of pemirolast on the release of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP) from human eosinophils. Calcium ionophore A23187 caused both LTC4 and ECP release from human eosinophils, whereas PAF and FMLP induced only ECP release from the eosinophils. Pemirolast (10(-6) to 10(-3) M) inhibited A23187-induced LTC4 release from the eosinophils in a dose-dependent fashion with 77% inhibition at 10(-3) M. Pemirolast (10(-5) to 10(-3) M) inhibited A23187-induced ECP release from the eosinophils in a dose-dependent fashion with 42% inhibition at 10(-3) M. Pemirolast (10(-4) and 10(-3) M) also inhibited PAF-induced and FMLP-induced ECP release from the eosinophils. We conclude that pemirolast prevents the activation of human eosinophils to inhibit LTC4 and ECP release. These results suggest that pemirolast might be useful in controlling allergic diseases by inhibiting eosinophil activation.
Kawashima
T
T
Research Laboratories, Tokyo Tanabe Co. Ltd., Japan.
Iwamoto
I
I
Nakagawa
N
N
Tomioka
H
H
Yoshida
S
S
D001249:Asthma / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D012260:Ribonucleases; D012636:Secretory Rate / Q000187:drug effects
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D010972:Platelet Activating Factor; D011725:Pyridines; D011744:Pyrimidinones; C055139:pemirolast; D017997:Leukotriene C4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012260:Ribonucleases