Characteristics of norepinephrine and clonidine displacement of [H-3]yohimbine binding to platelet alpha(2)-adrenoreceptors in healthy volunteers

Clonidine's estimates of platelet alpha(2)-adrenoreceptor (alpha(2)AR) dens ity are substantially lower than yohimbine's. This discrepancy could have c ontributed to inconsistent results from studies on the role of alpha(2)AR i n depression. Furthermore, few studies have investigated the relative distr ibution of alpha(2)AR between the high- and low-affinity states or their G( i) protein coupling. [H-3](y)ohimbine saturable binding to platelet alpha(2 )AR, its displacement by norepinephrine and clonidine, and the effects of G pp(NH)p on agonist displacement curves were investigated in 11 healthy volu nteers. Clonidine estimates of alpha(2)AR density were close to norepinephr ine estimates, and both were strongly correlated. Clonidine's K-L/K-H ratio was lower than norepinephrine's, consistent with its partial agonist natur e. Norepinephrine and clonidine displacement curves revealed two affinity s tates. Gpp(NH)p induced a significant rightward shift to a single low-affin ity state. When used in combination with a specific antagonist, clonidine's estimates of alpha(2)AR density were similar to those of norepinephrine's, and both were higher than previously reported, when clonidine was used alo ne. Re-evaluation of previous studies on alpha(2)AR in depression using clo nidine is needed. The combined use of antagonist-saturation and agonist-dis placement experiments to examine possible dysregulation in alpha(2)AR coupl ing to G(i) protein in psychiatric disorders is recommended. (C) 1999 Elsev ier Science Ireland Ltd. All rights reserved.