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

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 a high affinity and presents the pharmacological specificity corresponding to the peripheral binding sites (PK 11195 greater than RO5-4864 greater than diazepam greater than 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 (KD and Bmax) for [3H]PK 11195 between normotensive and hypertensive subjects. The very high binding capacity of human and rat platelets (Bmax greater than pmole/10(8) cells) makes them a good biological model for studying the physiological significance of "peripheral type" benzodiazepine binding sites.