Overexpression of histamine H4 receptors in the kidney of diabetic rat

The renal expression of H-1 and H-2 receptors has previously been demonstrated, while that of the H-4 receptor has been poorly investigated, and thus the aim of this research was to investigate the expression of the H-4 receptor in the kidney of diabetic rats. 24 8-week-old male Wistar rats. Diabetes was induced in 12 rats by a single intravenous injection of streptozotocin, and animals were killed 6 weeks later. Kidneys were collected and processed for quantitative PCR or immunohistochemical analyses. To ascertain the renal topology of the H-4 receptor, colocalization experiments were performed with a series of markers. H-4 receptor is expressed in healthy rats, although at a very low level, and is strongly upregulated in diabetic animals. Immunohistochemical analysis revealed the highest immune-positivity in the medulla. Colocalization experiments revealed a close overlap in expression topology of the H-4 receptor and both Tamm-Horsfall glycoprotein and aquaporin 1 was observed. The results demonstrate, for the first time, that the H-4 receptor is expressed in the kidney mainly by resident renal cells of the loop of Henl, and that this receptor is significantly overexpressed in diabetic animals, thus suggesting a possible role in the pathogenesis of diabetes-associated renal disease.