DOWN-REGULATION OF HEPATIC PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS CAUSED BY ACUTE LEAD-INTOXICATION

In the present study we investigated the influence of acute lead poiso ning upon the expression of benzodiazepine receptors. In addition, we examined if administration of PK 11195, an isoquinoline carboxamide de rivative, to lead-poisoned rats could modulate the changes in receptor binding properties achieved by lead alone. Lead poisoning was ascerta ined by determination of urine delta-aminolevulinic acid levels and le ad levels in rat livers. Scatchard analysis of saturation curves of [H -3]PK 11195 binding to liver membranes of rats treated with lead alone or with both lead and PK 11195 showed an approximately two-fold decre ase in receptor density in comparison with control groups. Peripheral benzodiazepine receptor density in the kidneys and adrenals of poisone d rats was not changed by lead intoxication per se or by coadministrat ion of PK 11195. Scatchard analysis of saturation curves of [H-3]Ro 15 -1788 binding in rat cerebral cortex tissue showed no difference in th e receptor density between the various groups. The K-d values of all o rgans were in the nanomolar range (1-4 nM). We conclude that PK 11195 is not a protective agent of hepatic peripheral benzodiazepine recepto rs in lead intoxication. Moreover, it causes over-accumulation of lead in hepatocytes in an unknown mechanism of action.