Generation and characterisation of the first anti-human H3R445/453 isoform specific antibody probe

Abstract

The H3 receptor subtype is a classic G-protein coupled receptor (GPCR) expressed almost exclusively in the CNS. The existence of multiple H3R isoform mRNA has opened up possibilities to account for the pharmacological heterogeneity inH3R, within and across species, which has long been recognised, reviewed in [1, 2]. The full length clone is found in most abundance in the CNS in all species studied so far, however there is regional variation in the distribution of the different isoform mRNAs [3, 4]. This has given rise to speculation that H3R heterogeneity could underlie different activities and functions of the H3 R in specific brain regions. Furthermore, there is growing evidence that heteroligomerisation of H3 isoforms may occur and yield a novel regulatory mechanism [5]. H3R ligands may interact with multiple H3 isoforms in vivo so the signalling and functional properties of the isoforms need to be characterised. In order to define the importance of human H3 receptor heterogeneity, isoform specific immunological probes are required. Herein, we provide information on a new anti-human H3R445/453 receptor isoform specific antibody.