Interactions between nitrogen oxide-containing compounds and peripheral benzodiazepine receptors

• Published in: FEBS letters Vol. 260; no. 2; pp. 169 - 172
• Main Authors: Weissman, Ben A., Bolger, Gordon T., Chiang, Peter K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 29-01-1990; Elsevier
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Benzodiazepine receptor, peripheral; Benzodiazepinones - metabolism; Binding, Competitive; Biological and medical sciences; Calcium - metabolism; Calcium Channels - metabolism; Cardiovascular system; Cell Membrane - drug effects; Cell Membrane - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Ferricyanides - pharmacology; Guinea pig heart; Guinea Pigs; Heart - drug effects; Heart Rate - drug effects; Kidney - drug effects; Kidney - metabolism; Medical sciences; Miscellaneous; Myocardium - metabolism; nitrogen oxide; Nitroprusside - pharmacology; Pharmacology. Drug treatments; plasma membranes; Rat atrium; Rats; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; Sodium nitroprusside; Sodium nitroprusside; Benzodiazepine receptor, peripheral; Guinea pig heart; Rat atrium; Heart; Vertebrata; Mammalia; Guinea pig; Vasodilator agent; Animal; Rodentia; Organic nitrate; Benzodiazepine receptor; Mechanism of action; In vitro
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(90)80095-Z

Nitrogen oxide-containing compounds displaced the peripheral benzodiazepine ligand [
3H]Ro5-4864 from guinea pig membrane preparations. Sodium nitroprusside (SNP) was the most potent (
IC
50 = 5.61 ± 1.72 × 10
−5 M). Moreover, its ability to bind to these receptors showed marked tissue variability (heart > kidney ⪢ 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.