Gnm. Gurguis et al., Characteristics of norepinephrine and clonidine displacement of [H-3]yohimbine binding to platelet alpha(2)-adrenoreceptors in healthy volunteers, PSYCHIAT R, 85(3), 1999, pp. 305-314
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.