Role of Src in hypersensitization to phosphodiesterase inhibitors in beta2-adrenoceptor-desensitized eosinophils.
When guinea pig eosinophils were incubated with fenoterol, a beta2-agonist, for 120 min, not only desensitization of beta2-adrenoceptors but also hyperresponsiveness to phosphodiesterase (PDE) inhibitors, such as theophylline and rolipram, was observed. The fenoterol-induced beta2-adrenoceptor desensitization was not affected by pretreatment with either genistein, a broad-spectrum tyrosine kinase inhibitor, or PP2, a specific Src family tyrosine kinase inhibitor. On the other hand, both genistein and PP2 abolished the hyperresponsiveness to PDE inhibitors in beta2-adrenoceptor-desensitized eosinophils. These findings suggested that Src family tyrosine kinases play important roles in the hypersensitization of PDE to PDE inhibitors in beta2-adrenoceptor-desensitized eosinophils.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan.
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Kirino
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Mio
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Fujii
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Kamei
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D005280:Fenoterol / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D019061:src-Family Kinases / Q000502:physiology*
C412373:AG 1879; D000318:Adrenergic beta-Agonists; D007476:Ionophores; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D018343:Receptors, Adrenergic, beta-2; D005280:Fenoterol; D000001:Calcimycin; D019833:Genistein; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D019061:src-Family Kinases