PERIPHERAL BENZODIAZEPINE RECEPTORS - MOLECULAR PHARMACOLOGY TO POSSIBLE PHYSIOLOGICAL SIGNIFICANCE IN STRESS-INDUCED HYPERTENSION

Simultaneous to the discovery of binding sites for benzodiazepines in the central nervous system (CNS) was the observation that [H-3]diazepa m also bound to sites in peripheral tissues, including liver, heart, l ung, adrenal, and kidney. These ''peripheral'' benzodiazepine receptor s (PER) have been well characterized, but their physiological signific ance remains elusive. Researchers have discovered candidates that may serve as endogenous ligands for the PER. The PER is both tonically and phasically regulated by neural and hormonal mechanisms. This site als o 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 regulati on of renal PER coupled with the pharmacological simulation of these e ffects by angiotensin II suggest that the physiological significance o f this site in kidney may be related to the pathophysiology of hyperte nsion. The potential relevance of these findings for the development o f novel pharmacotherapies for stress-related disorders in humans such as hypertension is discussed.