Characterization of peripheral type benzodiazepine binding sites in human and rat platelets by using [ 3H]PK 11195. Studies in hypertensive patients

Abstract

Peripheral type benzodiazepine binding sites have been studied in human and rat platelets and platelet membranes by using PK 11195 (1-(2-chlorophenyl)- N-methyl- N-(1-methyl propyl)-3-isoquinolinecarboxamide) as a ligand. [ 3H]PK 11195 binding to the intact cells and membranes is saturable, with high affinity and presents the pharmacological specificity corresponding to the peripheral binding sites (PK 11195 > RO5–4864 > diazepam > clonazepam). [ 3H]PK 11195 affinity is not affected by cell lysis, but there is a loss of binding capacity, contrarily to RO5–4864 whose affinity is greatly diminished. For this reason [ 3H]RO5–4864 binding can only be demonstrated in intact cells. Furthermore opposite to RO5–4864, PK 11195 affinity is not decreased by increasing temperatures. No difference was found between binding parameters ( K D and B max) for [ 3H]PK 11195 between normotensive and hypertensive subjects. The very high binding capacity of human and rat platelets ( B max > pmole/10 8 cells) makes them a good biological model for studying the physiological significance of “peripheral type” benzodiazepine binding sites.