Regulatory mechanism of eosinophil peroxidase release from guinea pig eosinophils.
The regulatory mechanism of degranulation of guinea pig peritoneal eosinophils was studied by determination of eosinophil peroxidase (EPO) release. Beta-agonists, such as isoproterenol, salbutamol and fenoterol, effectively inhibited A23187-induced EPO release from guinea pig eosinophils. The inhibitory effects of beta-agonists were attenuated by pretreatment with either propranolol, a non-selective beta-antagonist, or ICI 118,551, a selective beta2-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. Beta-agonists and theophylline were effective in inhibiting degranulation of eosinophils by increasing intracellular cAMP level coupled with the activation of protein kinase A.
Kirino
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Mio
M
M
Kamei
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology*; D006168:Guinea Pigs; D007476:Ionophores / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010544:Peroxidases / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D007476:Ionophores; D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D; D000001:Calcimycin; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D002118:Calcium