Peripheral-type
benzodiazepine receptors (PBRs) are abundant in the cardiovascular system. In the cardiovascular lumen, PBRs are present in platelets, erythrocytes, lymphocytes, and mononuclear cells. In the walls of the cardiovascular system, PBR can be found in the endothelium, the striated cardiac muscle, the vascular smooth muscles, and the mast cells. The subcellular location of PBR is primarily in mitochondria. The PBR complex includes the
isoquinoline binding protein (
IBP),
voltage-dependent anion channel (VDAC), and
adenine nucleotide transporter (ANT). Putative endogenous
ligands for PBR include
protoporphyrin IX,
diazepam binding inhibitor (
DBI),
triakontatetraneuropeptide (TTN), and
phospholipase A2 (PLA2). Classical synthetic
ligands for PBR are the
isoquinoline 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinolinecarboxamide (
PK 11195) and the
benzodiazepine 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (Ro5 4864). Novel PBR
ligands include N,N-di-n-hexyl 2-(4-fluorophenyl)indole-3-acetamide (FGIN-1-27) and 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]
indole-1-
acetamide (
SSR180575), both possessing steroidogenic properties, but while
FGIN-1-27 is pro-apoptotic,
SSR180575 is anti-apoptotic. Putative PBR functions include regulation of steroidogenesis, apoptosis, cell proliferation, the mitochondrial membrane potential, the mitochondrial respiratory chain,
voltage-dependent calcium channels, responses to stress, and microglial activation. PBRs in blood vessel walls appear to take part in responses to
trauma such as
ischemia. The irreversible PBR antagonist,
SSR180575, was found to reduce damage correlated with
ischemia. Stress,
anxiety disorders, and
neurological disorders, as well as their treatment, can affect PBR levels in blood cells. PBRs in blood cells appear to play roles in several aspects of the immune response, such as phagocytosis and the secretion of
interleukin-2,
interleukin-3, and
immunoglobulin A (
IgA). Thus, alterations in PBR density in blood cells may have immunological consequences in the affected person. In conclusion, PBR in the cardiovascular system may represent a new target for
drug development.