Abstract
Formyl peptides activate superoxide anion (O2 −) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O2 − formation via H2-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H2-receptor agonists in the guinea pig atrium, on O2 − formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O2 − formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 μmol/l inhibited and, at concentrations above 30 μmol/l, enhanced formyl peptide-induce O2 − formation in neutrophils. In HL-60 cells, guanidines per se activated O2 − formation. The stimulatory effects of guanidines on O2 − formation were not inhibited by H1- or H2-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and Gi/Go-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O −2 formation.
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Hagelüken, A., Burde, R., Nürnberg, B. et al. Cationic-amphiphilic arpromidine-derived guanidines and a histamine trifluoromethyl-toluidide derivative may activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism. Naunyn-Schmiedeberg's Arch Pharmacol 351, 305–308 (1995). https://doi.org/10.1007/BF00233251
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DOI: https://doi.org/10.1007/BF00233251