High constitutive activity of native H3 receptors regulates histamine neurons in brain. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Année : 2000

High constitutive activity of native H3 receptors regulates histamine neurons in brain.

A. Rouleau
  • Fonction : Auteur
X Ligneau
  • Fonction : Auteur
F Gbahou
  • Fonction : Auteur
J. Tardivel-Lacombe
  • Fonction : Auteur
H. Stark
  • Fonction : Auteur
W Schunack
  • Fonction : Auteur
C Ganellin
  • Fonction : Auteur
J. Schwartz
  • Fonction : Auteur
J Arrang
  • Fonction : Auteur

Résumé

Some G-protein-coupled receptors display 'constitutive activity', that is, spontaneous activity in the absence of agonist. This means that a proportion of the receptor population spontaneously undergoes an allosteric transition, leading to a conformation that can bind G proteins. The process has been shown to occur with recombinant receptors expressed at high density, and/or mutated, but also non-mutated recombinant receptors expressed at physiological concentrations. Transgenic mice that express a constitutively active mutant of the beta2-adrenergic receptor display cardiac anomalies; and spontaneous receptor mutations leading to constitutive activity are at the origin of some human diseases. Nevertheless, this process has not previously been found to occur in animals expressing normal levels of receptor. Here we show that two isoforms of the recombinant rat H3 receptor display high constitutive activity. Using drugs that abrogate this activity ('inverse agonists') and a drug that opposes both agonists and inverse agonists ('neutral antagonist'), we show that constitutive activity of native H3 receptors is present in rodent brain and that it controls histaminergic neuron activity in vivo. Inverse agonists may therefore find therapeutic applications, even in the case of diseases involving non-mutated receptors expressed at normal levels.
Fichier non déposé

Dates et versions

hal-02081523 , version 1 (27-03-2019)

Identifiants

Citer

S. Morisset, A. Rouleau, X Ligneau, F Gbahou, J. Tardivel-Lacombe, et al.. High constitutive activity of native H3 receptors regulates histamine neurons in brain.. Nature, 2000, 408 (6814), pp.860-4. ⟨10.1038/35048583⟩. ⟨hal-02081523⟩
11 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More