Peripheral benzodiazepine receptors: molecular pharmacology to possible physiological significance in stress-induced hypertension

Clinical Neuropharmacology
R C Drugan

Abstract

Simultaneous to the discovery of binding sites for benzodiazepines in the central nervous system (CNS) was the observation that [3H]diazepam also bound to sites in peripheral tissues, including liver, heart, lung, adrenal, and kidney. These "peripheral" benzodiazepine receptors (PBR) have been well characterized, but their physiological significance remains elusive. Researchers have discovered candidates that may serve as endogenous ligands for the PBR. The PBR is both tonically and phasically regulated by neural and hormonal mechanisms. This site also appears to be a critical factor in the rate-limiting step of steroid synthesis, the conversion of cholesterol to pregnenolone in a variety of tissues. In addition, the tissue-specific, stress-induced regulation of renal PBR coupled with the pharmacological simulation of these effects by angiotensin II suggest that the physiological significance of this site in kidney may be related to the pathophysiology of hypertension. The potential relevance of these findings for the development of novel pharmacotherapies for stress-related disorders in humans such as hypertension is discussed.

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