Interactions between nitrogen oxide-containing compounds and peripheral benzodiazepine receptors.
Nitrogen oxide-containing compounds displaced the peripheral benzodiazepine ligand [3H]Ro5-4864 from guinea pig membrane preparations. Sodium nitroprusside (SNP) was the most potent (IC50 = 5.61 +/- 1.72 x 10(-5) M). Moreover, its ability to bind to these receptors showed marked tissue variability (heart greater than kidney much greater than cerebral cortex). When tested on rat atrium, SNP by itself had no effect on basal inotropy or the increase in inotropy induced by (-)-S-BAY K 8644. In contrast, Ro5-4864 potentiated the marked increase in inotropy induced by (-)-S-Bay K 8644, and SNP completely abolished the potentiation of inotropy observed with Ro5-4864. Since peripheral benzodiazepine receptors are associated with calcium mobilization in the heart, these findings may indicate that some of the clinical effects of nitric oxide-generating drugs could be mediated by these receptors.
Weissman
B A
BA
Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Bolger
G T
GT
Chiang
P K
PK
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism*; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005292:Ferricyanides / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
D001570:Benzodiazepinones; D015220:Calcium Channels; D005292:Ferricyanides; D011963:Receptors, GABA-A; D009599:Nitroprusside; C028513:4'-chlorodiazepam; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium