Characteristics of norepinephrine and clonidine displacement of [3H]yohimbine binding to platelet alpha2-adrenoreceptors in healthy volunteers

George N M Gurguis, Stephanie P. Vo, Jaishri Blakeley, Paul J. Orsulak, A. John Rush

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Clonidine's estimates of platelet α2-adrenoreceptor (α2AR) density are substantially lower than yohimbine's. This discrepancy could have contributed to inconsistent results from studies on the role of α2AR in depression. Furthermore, few studies have investigated the relative distribution of α2AR between the high- and low-affinity states or their G(i) protein coupling. [3H](y)ohimbine saturable binding to platelet α2AR, its displacement by norepinephrine and clonidine, and the effects of Gpp(NH)p on agonist displacement curves were investigated in 11 healthy volunteers. Clonidine estimates of α2AR density were close to norepinephrine estimates, and both were strongly correlated. Clonidine's K(L)/K(H) ratio was lower than norepinephrine's, consistent with its partial agonist nature. Norepinephrine and clonidine displacement curves revealed two affinity states. Gpp(NH)p induced a significant rightward shift to a single low-affinity state. When used in combination with a specific antagonist, clonidine's estimates of α2AR density were similar to those of norepinephrine's, and both were higher than previously reported, when clonidine was used alone. Re-evaluation of previous studies on α2AR in depression using clonidine is needed. The combined use of antagonist-saturation and agonist-displacement experiments to examine possible dysregulation in α2AR coupling to G(i) protein in psychiatric-disorders is recommended.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalPsychiatry research
Volume85
Issue number3
DOIs
StatePublished - Mar 22 1999

Keywords

  • Adrenergic receptors
  • Anxiety
  • Coupling
  • Depression
  • G protein
  • Platelets

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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