Histamine H-receptor-mediated modulation of NMDA receptors signaling responses.

This study attempted to clarify the role of histamine H receptors in epilepsy by exploring the effects of agonists and inverse agonists on the rundown of the current induced by iterative applications of NMDA or GABA in primary neuronal culture. Mepyramine, a classical H-receptor antagonist/inverse agonist, increased the NMDA current by about 40% during the first minutes of recording. This effect was concentration-dependent, maximal at 10 nM, and mimicked by triprolidine, another antagonist/inverse agonist.

BRET Analysis of GPCR Dimers in Neurons and Non-Neuronal Cells: Evidence for Inactive, Agonist, and Constitutive Conformations.

G-protein-coupled receptors (GPCRs) are dimeric proteins, but the functional consequences of the process are still debated. Active GPCR conformations are promoted either by agonists or constitutive activity. Inverse agonists decrease constitutive activity by promoting inactive conformations.

Molecular dynamics of the histamine H3 membrane receptor reveals different mechanisms of GPCR signal transduction.

In this work, we studied the mechanisms of classical activation and inactivation of signal transduction by the histamine H3 receptor, a 7-helix transmembrane bundle G-Protein Coupled Receptor through long-time-scale atomistic molecular dynamics simulations of the receptor embedded in a hydrated double layer of dipalmitoyl phosphatidyl choline, a zwitterionic polysaturated ordered lipid. Three systems were prepared: the apo receptor, representing the constitutively active receptor; and two holo-receptors-the receptor coupled to the antagonist/inverse agonist ciproxifan, representing the inactive state of the receptor, and the receptor coupled to the endogenous agonist histamine and representing the active state of the receptor. An extensive analysis of the simulation showed that the three states of H3R present significant structural and dynamical differences as well as a complex behavior given that the measured properties interact in multiple and interdependent ways.

Mechanistic characterization of S 38093, a novel inverse agonist at histamine H3 receptors.

Histaminergic H3 inverse agonists, by stimulating central histamine release, represent attractive drug candidates to treat cognitive disorders. The present studies aimed to describe the mechanistic profile of S 38093 a novel H3 receptors inverse agonist. S 38093 displays a moderate affinity for rat, mouse and human H3 receptors (Ki=8.