Identification of a histamine H3-like receptor in the zebrafish (Danio rerio) brain

The distribution of histaminergic fibers in the zebrafish brain was recently shown to resemble that in mammals. Expression of L-histidine decarboxylase (HDC) mRNA was shown only in the area corresponding to that expressing HDC in mammals. This indicates that the zebrafish could be a useful model for studies on the function of the brain histaminergic system. in this study an H-3-like receptor is identified in zebrafish brain. With binding studies using N-alpha-[H-3]methylhistamine on zebrafish brain sections, signals were observed in several regions. Highest densities were detected in optic tectum and hypothalamus. The autoradiographic signal was abolished completely by the H-3-specific antagonist clobenpropit and significantly reduced by another H-3 antagonist, thioperamide. Histamine and immepip induced an increase of guanosine 5'-(gamma-[S-35]thio)triphosphate binding in several areas of the zebrafish brain. The activation was blocked with clobenpropit but not with cimetidine or mepyramine. These results indicate that the zebrafish has a histamine H-3-like receptor that functionally interacts with the inhibitory, G(i)/G(o), class of G proteins. No previous evidence for a histamine receptor in zebrafish exists. The receptor described here is apparently similar to the mammalian H-3 receptor, making this the first description of a histamine H-3-like receptor in a lower vertebrate.