Expression of orexin-A and orexin receptors in the kidney and the presence of orexin-A-like immunoreactivity in human urine.
Orexin-A (hypocretin-1), a neuropeptide with stimulatory actions on arousal and appetite, was originally shown to be specifically expressed in the hypothalamus. We studied expression of orexin-A and orexin receptors in the kidney and the presence of orexin-A-like immunoreactivity in human urine. Immunocytochemistry showed that orexin-A-like immunoreactivity and two types of orexin receptors (types 1 and 2) were localized in the tubules of the human kidney obtained at autopsy. Orexin-A-like immunoreactivity was detected in human kidneys (21.3 +/- 6.2 fmol/g wet weight, mean +/- S.E.M., n = 4) and rat kidneys (16.2 +/- 1.6 fmol/g wet weight, n = 5) by radioimmunoassay, although the levels were much lower than the levels in the brain. Orexin-A-like immunoreactivity was present in the urine obtained from male healthy volunteers (67.8 +/- 4.5 pmol/l, n = 5). Reverse phase high-performance liquid chromatography showed that most of orexin-A-like immunoreactivity of the urine extract was eluted earlier than authentic orexin-A, suggesting that orexin-A-like immunoreactivity in urine was modified to hydrophilic forms. Reverse transcriptase polymerase chain reaction showed expression of orexin receptors 1 and 2 mRNAs in the human kidney. These findings suggest that orexin-A is produced by the renal tubular cells and secreted into urine. Orexin-A may act on the kidney in the autocrine or paracrine fashion, or via the urine (urocrine fashion).
Takahashi
Kazuhiro
K
Department of Analytical Medical Technology, Tohoku University School of Health Sciences, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. ktaka-md@mail.tains.tohuku.ac.jp
Arihara
Zenei
Z
Suzuki
Takashi
T
Sone
Masahiko
M
Kikuchi
Kumi
K
Sasano
Hironobu
H
Murakami
Osamu
O
Totsune
Kazuhito
K
D000328:Adult; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology / Q000652:urine*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000032:analysis* / Q000235:genetics / Q000276:immunology / Q000652:urine*; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000032:analysis / Q000378:metabolism*; D051437:Renal Insufficiency
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide