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Interactions between nitrogen oxide-containing compounds and peripheral benzodiazepine receptors
B A Weissman1, G T Bolger, P K Chiang
1Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
FEBS Letters
|January 29, 1990
Summary
Nitric oxide compounds interact with peripheral benzodiazepine receptors, particularly in the heart. Sodium nitroprusside
Area of Science:
- Pharmacology
- Neuroscience
- Cardiovascular Research
Background:
- Peripheral benzodiazepine receptors (PBPRs) are implicated in cellular processes.
- Nitric oxide (NO) plays a role in cardiovascular function.
- The interaction between NO-releasing agents and PBPRs is not well understood.
Purpose of the Study:
- To investigate the interaction between nitrogen oxide-containing compounds and peripheral benzodiazepine receptors.
- To explore the functional consequences of this interaction in cardiac tissue.
Main Methods:
- Competitive binding assays using [3H]Ro5-4864 to measure displacement by NO-containing compounds.
- In vitro studies on rat atrial preparations to assess effects on inotropy.
- Evaluation of the modulatory effects of sodium nitroprusside (SNP) and Ro5-4864 on cardiac contractility.
Main Results:
- Nitrogen oxide-containing compounds, notably sodium nitroprusside (SNP), displaced the PBPR ligand [3H]Ro5-4864.
- SNP demonstrated potent binding to PBPRs with significant tissue variability (heart > kidney > cerebral cortex).
- SNP abolished the potentiation of inotropy by Ro5-4864 in rat atria, suggesting a functional interaction.
Conclusions:
- Nitrogen oxide compounds bind to peripheral benzodiazepine receptors.
- These interactions, particularly with SNP, can modulate cardiac contractility.
- Clinical effects of nitric oxide-generating drugs may involve peripheral benzodiazepine receptor pathways.