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 ( 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.