title: Divergent effects of propranolol on neutrophil superoxide release: involvement of phosphatidic acid and diacylglycerol as second messengers.
abstract: Relatively high levels of propranolol (170 microM) markedly attenuated the generation of 1,2 diacylglycerol in neutrophils stimulated with either FMLP plus cytochalasin B or with 20.0 mM NaF. This effect resulted from inhibition of phosphatidic acid phosphohydrolase as it was accompanied by a corresponding increase in the recovery of phosphatidic acid in organic extracts of stimulated cells. Although propranolol enhanced phosphatidic acid levels in neutrophils treated with FMLP alone, the drug had only a slight inhibitory influence on diglyceride generation in these cells. The effect of propranolol on enhancement of PA levels in neutrophils treated with FMLP alone strongly correlated with enhancement of FMLP-induced O2- generation. However, propranolol induced a similar dose-dependent inhibition of O2- generation in neutrophils stimulated with either FMLP + cytochalasin B or with 20.0 mM NaF. These results are consistent with the hypothesis that both phosphatidic acid and diacylglycerol are required for optimal initiation of neutrophil O2- release.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
authors.forename: D
authors.initials: D
authors.lastname: English
authors.forename: G S
authors.initials: GS
authors.lastname: Taylor
mesh_terms: D003571:Cytochalasin B / Q000494:pharmacology; D004075:Diglycerides / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010712:Phosphatidic Acids / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D010712:Phosphatidic Acids; D013481:Superoxides; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011433:Propranolol; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases