Transient catecholamine modulation of neutrophil activation: kinetic and intracellular aspects of isoproterenol action.
Modulation of neutrophil activation by catecholamines may reflect regulatory mechanisms that couple beta-adrenergic and N-formyl peptide receptors to antagonistic biochemical pathways. We examined kinetic and mechanistic aspects of the inhibition by catecholamines of neutrophil activation by formyl peptides. Inhibition of oxidant production by isoproterenol (ISO) was detected as low as 3 nM, had an ID50 of 10(-7) M, and could be blocked and reversed by propranolol. Recovery of cell function occurred over a period of minutes when the concentration of ISO was less than 10(-6) M. These observations are discussed in terms of the interaction of ISO with the adrenergic receptors. The site of catecholamine action is addressed. ISO neither influences formyl peptide-receptor interaction nor does it inhibit oxidant production by phorbol ester. These results suggest an impairment of intracellular signalling processes that couple the formyl peptide-receptor binding to cell activation. We observed inhibition of intracellular Ca++ elevation by ISO only at low formyl peptide concentrations. This inhibition is consistent with a partial inhibition of phosphoinositide metabolism, which was observed. Several other cell responses, including actin polymerization and right angle light scatter, are minimally inhibited by 10(-6) M ISO indicating that the cell activation process is not entirely obliterated. The presence of catecholamine and formyl peptide results in a synergistic elevation of cAMP. The intracellular targets of ISO action may be regulated by cAMP dependent kinases and could follow a branchpoint in the activation sequence that leads distinctly to oxidase activation and cytoskeletal activation.
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D000199:Actins; D002395:Catecholamines; D010716:Phosphatidylinositols; D011943:Receptors, Adrenergic, beta; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine