Human stanniocalcin inhibits renal phosphate excretion in the rat.
Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes where it counteracts hypercalcemia by inhibiting gill calcium uptake and stimulating renal inorganic phosphate (Pi) reabsorption. Human STC (hSTC) has recently been cloned and sequenced and is highly homologous to the fish hormone at the amino acid level. The objective of this study was to examine the possible effects of hSTC on electrolyte homeostasis and renal function in the rat. Recombinant hSTC was expressed in bacteria and purified by metal-ion affinity chromatography and reverse-phase high performance liquid chromatography. Anesthetized animals were given bolus infusions of 1, 5, or 10 nmol hSTC per kilogram of body weight. Control animals received solvent alone. The most effective dosage was 5 nmol/kg, which caused significant reductions in both absolute and fractional phosphate excretion in comparison with control rats. The hSTC had no effect on the renal excretion of other ions, the glomerular filtration rate, renal blood flow, blood pressure, or plasma electrolytes (Na+, K+, Ca2+, Pi, Mg/+). The maximum effect of hSTC on phosphate excretion was observed 60-80 minutes postinjection. Lesser effects were obtained with higher and lower dosages of hormone. When renal cortical brush-border membrane vesicles were isolated from control and hormone-treated animals 80 minutes postinjection, the rate of Na+/Pi cotransport was found to be 40% higher in vesicles from hormone-treated animals (p < 0.01; 5 nmol hSTC/kg). Together, the renal clearance and membrane vesicle data indicate that hSTC participates in the renal regulation of Pi homeostasis in mammals.
Wagner
G F
GF
Department of Physiology, Faculty of Medicine, University of Western Ontario, London, Canada.
Vozzolo
B L
BL
Jaworski
E
E
Haddad
M
M
Kline
R L
RL
Olsen
H S
HS
Rosen
C A
CA
Davidson
M B
MB
Renfro
J L
JL
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004573:Electrolytes / Q000097:blood / Q000652:urine; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D006728:Hormones / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010710:Phosphates / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D004573:Electrolytes; D006023:Glycoproteins; D006728:Hormones; D010710:Phosphates; C051795:teleocalcin