Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues.
BACKGROUND
Urotensin-II (UII), a cyclic dodecapeptide originally isolated from fish urophysis that has potent cardiovascular effects, has recently been identified as an endogenous ligand for the orphan G protein-coupled receptor, GPR14. The physiological roles of endogenous UII and its receptor in humans remain unknown.


OBJECTIVE
To investigate the presence of human (h) UII-like immunoreactivity (hUII-LI) in human biological fluids, and the expression of hUII and GPR14 genes in human tissues.


METHODS
We have established a specific radioimmunoassay for hUII and the real-time quantitative reverse transcriptase polymerase chain reaction method using LightCycler for the quantification of hUII and GPR14 mRNAs.


RESULTS
Gel filtration and reverse-phase high performance liquid chromatography of human urine extracts revealed a single major peak of hUII-LI co-eluting with known hUII. The concentrations of hUII-LI in urine from normal individuals were 7.4 +/- 0.9 microg/g creatinine, whereas its plasma concentration was undetectable (< 50 pg/ml). Urinary hUII concentrations from patients with essential hypertension and those with renal tubular abnormality, but not with glomerular diseases, were significantly greater than those from normal individuals. The resulting fractional excretion of hUII, exceeding the glomerular filtration rate, suggests a renal origin of urinary UII-LI. hUII mRNAs were abundantly expressed in the kidney and the right atrium, but far less so in the vasculature, whereas GPR14 mRNAs were equally and abundantly expressed in both cardiovascular and renal tissues.


CONCLUSIONS
These data suggest that urinary hUII is derived mainly from a renal source, and that hUII functions as an autocrine/paracrine vasoactive factor not only in the cardiovascular system, but also in the kidney, with an as yet unspecified function.
Matsushita
M
M
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Shichiri
M
M
Imai
T
T
Iwashina
M
M
Tanaka
H
H
Takasu
N
N
Hirata
Y
Y
D000328:Adult; D002319:Cardiovascular System / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014579:Urotensins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000652:urine
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II