Jpn. J. Pharmacol. 83 (4), 293-299 (2000)

Regulatory Mechanism of Eosinophil Peroxidase Release
From Guinea Pig Eosinophils

Yasushi Kirino, Mitsunobu Mio and Chiaki Kamei*

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan
*╩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╩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╩A inhibitor. In addition, calphostin╩C as well as cytochalasin╩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╩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╩A.

Keywords: Eosinophil, Eosinophil peroxidase release, Calcium ionophore A23187, cAMP, Protein kinase╩A

Copyrightę The Japanese Pharmacological Society 2000

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