Portacaval anastomosis causes selective alterations of peripheral-type benzodiazepine receptor expression in rat brain and peripheral tissues

There is a growing body of evidence to suggest that peripheral-type benzodi azepine receptors (PTBRs) and their endogenous ligands are implicated in th e pathogenesis of end-organ failure in chronic liver disease. Portal-system ic encephalopathy, a major neuropsychiatric complication associated with ch ronic liver disease, results in activation of brain PTBR and probably in pe ripheral organs. In order to address these issues, PTBR mRNA was measured u sing semi-quantitative RT-PCR in extracts of cerebral cortex, kidney and te stis of rats four weeks after end-to-side portacaval anastomosis and sham-o peration (controls). Densities of PTBR sites were measured concomitantly by in vitro receptor binding using the selective PTBR ligand [H-3]PK11195. Po rtacaval shunting resulted in a 2 to 3-fold increase in expression of PTBR in brain and kidney and a 37% reduction in expression in testis. Densities of [H-3]PK11195 sites changed in parallel with the alterations of gene expr ession. These findings suggest that selective alterations of PTBR expressio n are implicated in the pathogenesis of peripheral tissue hypertrophy (kidn ey) and/or atrophy (testis) which accompanies portal-systemic shunting in c hronic liver failure. In brain, activation of PTBR could result in an incre ase in the production of neurosteroids with potent inhibitory action in the CNS, which could contribute to the pathogenesis of portal-systemic encepha lopathy. (C) 1999 Elsevier Science Ltd. All rights reserved.