부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejphar.2008.06.029 Byline: Kristoffer Sahlholm, Johanna Nilsson, Daniel Marcellino, Kjell Fuxe, Peter Arhem Keywords: Histamine H.sub.4 receptor; GIRK channel; Thioperamide; Clobenpropit; Xenopus oocyte; Voltage-clamp Abstract: The recently cloned histamine H.sub.4 receptor is expressed predominantly in haematopoietic cells and has been found to modulate the function of mast cells, eosinophils, dendritic cells and T lymphocytes. It represents an attractive target for pharmacological interventions against a number of inflammatory and autoimmune disorders. In the present work we used two-electrode voltage-clamp to demonstrate histamine H.sub.4 receptor modulation of G protein-coupled inward rectifier potassium (GIRK) channels heterologously expressed in Xenopus oocytes. In accordance with earlier findings in other effector systems, full agonism by histamine and (R)-[alpha]-methylhistamine, partial agonism by clobenpropit and inverse agonism by thioperamide were observed. Furthermore, in oocytes injected with low amounts of receptor cRNA, clobenpropit apparently acted as a neutral antagonist. We also used the high temporal resolution afforded by this system to study the differential time courses of response deactivation upon ligand washout for clobenpropit and (R)-[alpha]-methylhistamine. GIRK channels represent a novel effector system for histamine H.sub.4 receptor modulation, which may be of physiological relevance and prove useful in the development of compounds targeting this receptor. Author Affiliation: Department of Neuroscience, Karolinska Institutet, SE-117 77 Stockholm, Sweden Article History: Received 26 October 2007; Revised 27 May 2008; Accepted 5 June 2008