Effects of beta-adrenergic agonists on metabolic activations of human neutrophils.
Although effects of adrenergic agonists on metabolic activation of neutrophils have been studied for over a decade, amounts of released arachidonic acid and its metabolites from the cells activated by chemotactic peptide (FMLP) are so small that the results have been in conflict. In this study, we developed a method to obtain enough amount of arachidonic acid released to examine the action sites of adrenergic agonists with respects to the metabolic bursts of human neutrophils. First, superoxide generation from the cells was estimated and the results indicated that the adrenergic agonists, such as isoproterenol, salbutamol, procaterol and epinephrine, inhibited over 70% and 40% of the superoxide generation stimulated by FMLP and serum treated zymosan (STZ), respectively. Another metabolic activation, the release of arachidonic acid, was achieved by FMLP if the cells were incubated with merthiolate (20-80 microM), but the merthiolate-treatment was ineffective on the cells activated by calcium ionophore (A23187). Isoproterenol and epinephrine decreased the arachidonic acid release only when the cells were activated by FMLP in the presence of merthiolate. In spite of the fact that isoproterenol (1 and 10 microM) hardly inhibited the arachidonic acid release activated by A23187, formations of leukotrienes were decreased up to approximately 70% of control level. Intracellular calcium concentration elevated by FMLP was hardly diminished by isoproterenol and salbutamol. From these observations, it appears likely that adrenergic agonists attenuate the signal transmission process of FMLP at a post-receptor site of action at a step before the activation of protein kinase C or phospholipase A2.
Department of Toxicology, Niigata College of Pharmacy, Japan.
K
K
Taniguchi
Y
Y
Masuda
K
K
Takanaka
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013849:Thimerosal / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D015289:Leukotrienes; D013481:Superoxides; D013849:Thimerosal; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium