Differences in pharmacological properties of histamine H(3) receptor agonists and antagonists revealed at two human H (3) receptor isoforms.

摘要

Histamine H3 receptors (H3Rs) are G-protein coupled auto-and hetero-receptors that have been shown via preclinical models to play a role in cognition, sleep, and obesity through the modulation of neurotransmitter release [1]. The human histamine H3R exists as multiple splice isoforms, including the full length H3(445) and also H3(365), which lacks 80 amino acids from the third intracellular loop but is also highly expressed in multiple brain regions [2, 3]. The third intracellular loop of the H3R is postulated to play a major role in coupling to G-proteins and signal transduction pathways, hence deletions in this region may influence H3R function. We describe here the differential pharmacology of the human H3 (445) and H3 (365) receptor isoforms.