Yasushi Kirino, Mitsunobu Mio and Chiaki Kamei*
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama
University, Okayama 700-8530, Japan
*ﾊTo whom correspondence should be addressed.
Abstract: The regulatory mechanism of degranulation of guinea
pig peritoneal eosinophils was studied by determination of eosinophil peroxidase
(EPO) release. b-Agonists, such as isoproterenol,
salbutamol and fenoterol, effectively inhibited A23187-induced EPO release
from guinea pig eosinophils. The inhibitory effects of b-agonists
were attenuated by pretreatment with either propranolol, a non-selective
b-antagonist, or ICIﾊ118,551, a selective b2-antagonist.
Both theophylline and dibutyryl-cAMP (db-cAMP) also significantly inhibited
A23187-induced EPO release. The inhibition of EPO release induced by db-cAMP
was attenuated by pretreatment with KT5720, a protein kinaseﾊA inhibitor.
In addition, calphostinﾊC as well as cytochalasinﾊD effectively inhibited
A23187-induced EPO release. From the results of the present study, it was
concluded that an increase in intracellular Ca2+ concentration
may lead to exocytosis of eosinophil granules through activation of protein
kinaseﾊC and microfilaments. b-Agonists and theophylline
were effective in inhibiting degranulation of eosinophils by increasing
intracellular cAMP level coupled with the activation of protein kinaseﾊA.
Keywords: Eosinophil, Eosinophil peroxidase release, Calcium ionophore
A23187, cAMP, Protein kinaseﾊA