Olfactory signaling components and olfactory receptors are expressed in tubule cells of the human kidney

• Published in: Archives of biochemistry and biophysics 2016-11, Vol.610, p.8-15
• Main Authors: Kalbe, Benjamin, Schlimm, Marian, Wojcik, Sebastian, Philippou, Stathis, Maßberg, Désirée, Jansen, Fabian, Scholz, Paul, Luebbert, Hermann, Ubrig, Burkhard, Osterloh, Sabrina, Hatt, Hanns
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Calcium; Calcium - metabolism; Cell Line; Cytosol - metabolism; Gene Expression Regulation; GPCR; Humans; Immunohistochemistry; Kidney Tubules - cytology; Kidney Tubules - metabolism; Ligands; Neoplasm Proteins - metabolism; Olfactory receptors; Pentanoic Acids - chemistry; Physiology; Proximal tubule; Real-Time Polymerase Chain Reaction; Receptors, G-Protein-Coupled - metabolism; Receptors, Odorant - metabolism; Signal Transduction; Signaling
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2016.09.017

Cells of the renal tubule system are in direct contact with compounds dissolved in the urine, such as short chain fatty acids (SCFA). Murine OR78, a member of the olfactory receptor (OR) family, is involved in SCFA-related regulation of renal blood pressure in mice. It is still unclear whether OR signaling has an impact on human renal physiology. In our study, we showed that OR51E1 and OR11H7, both of which can be activated by the SCFA isovaleric acid, are expressed in the HK-2 human proximal tubule cell line. We observed a transient increase in intracellular Ca2+ when isovaleric acid and 4-methylvaleric acid were added to HK-2 cells. The isovaleric acid-induced response was dependent on extracellular Ca2+ and adenylyl cyclase (AC) activation. Furthermore, we demonstrated that the canonical olfactory signaling components Gαolf and ACIII are co-localized with OR51E1. The number of cells responding to isovaleric acid correlated with the presence of primary cilia on HK-2 cells. OR51E1 protein expression was confirmed in the tubule system of human kidney tissue. Our study is the first to show the expression of ORs and olfactory signaling components in human kidney cells. Additionally, we discuss ORs as potential modulators of the renal physiology. •Isovaleric acid (IVA) lead to increased Ca2+ levels in HK-2 cells.•OR51E1, OR11H7, Golf, and ACIII are expressed in HK-2 cells.•Isovaleric acid activates an adenylyl cyclase-mediated pathway.•Number of cells responding to IVA correlated with the presence of primary cilia.•OR51E1 was found at the protein level in human kidney tissue.