Histamine H4 receptors are present in the kidney of diabetic rats

Objective and design The renal expression of H1 and H2 receptors has previously been demonstrated, while that of the H4 receptor has been poorly investigated, and thus the aim of this research was to investigate the expression of the H4 receptor in the kidney of diabetic rats. Material or subjects 24 8-week-old male Wistar rats. Treatment Diabetes was induced in 12 rats by a single intravenous injection of streptozotocin, and animals were killed 6 weeks later. Methods Kidneys were collected and processed for quantitative PCR or immunohistochemical analyses. To ascertain the renal topology of the H4 receptor, colocal- ization experiments were performed with a series of markers. Results H4 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 topol- ogy of the H4 receptor and both Tamm–Horsfall glycoprotein and aquaporin 1 was observed. Conclusions The results demonstrate, for the first time, that the H4 receptor is expressed in the kidney mainly by resident renal cells of the loop of Henle ́ and that this receptor is significantly overexpressed in diabetic animals, thus suggesting a possible role in the pathogenesis of dia- betes-associated renal disease.