Thromboxane A(2) as a possible natural ligand for benzodiazepine receptors

Receptors for benzodiazepines have recently been found in the brain but the natural ligand which can occupy these receptors is unknown. In a rat vascular preparation diazepam and chloridiazepoxide were found to inhibit pressor responses to noradrenaline and angiotensin but not those to potassium and vasopressin with IC(50) concentrations similar to those reported for displacement of [(3)H]diazepam from brain receptors. Imidazole, an inhibitor of thromboxane A(2) synthesis had similar actions to the benzodiazepines. Interactions between imidazole and the benzodiazepines suggested that the latter may be competitive antagonists of thromboxane A(2). The possibility that thromboxane A(2) may be the natural ligand is supported by recent evidence that brain tissue contains high levels of this substance.