作者: Rahel Burde , Armin Buschauer , Roland Seifert
DOI: 10.1007/BF00176340
关键词:
摘要: Human neutrophils possess an NADPH oxidase which catalyzes superoxide (O inf2 sup− ) formation and is activated by chemotactic peptides. Histamine inhibits O sup−1 via H2-receptors (Burde et al. 1989). We characterized the neutrophil H2-receptor with a series of new guanidine-type H2-agonists structurally derived from impromidine. inhibited IC50 value 6.7 ± 1.2 μM. Five aryloxy- arylthioalkylguanidines were less potent effective than histamine. Several arpromidine-like phenyl(pyridylalkyl)guanidines either full or partial H2-agonists. Some guanidines three-membered carbon chain connecting aromatic rings guanidine group; they similarly as Shortening elongation substantially decreased potency intrinsic activity guanidines. Halogenation phenyl ring did not affect compounds in comparison to non-substituted parent compound. The H2-antagonist, famotidine, competitively antagonized inhibition caused guanidine, arpromidine, pA2 6.84. cimetidine, differentially counteracted Partial effects inhibitor phosphodiesterases, 3-isobutyl-lmethylxanthine, additively enhanced inhibitory histamine properties compared literature data concerning guinea pig atrium. In latter system, are potencies up 125-fold that Our indicate inhibit human H2-receptors. structure/activity relationship for differs one atrium, suggesting has cell type-specific properties. Other possibilities explain differences between these systems discussed.