Is big endothelin converted to endothelin-1 in circulating blood?
Although evidence has been accumulating to support an intracellular processing of big endothelin-1 (big ET-1) to ET-1, molecular conversion in the circulating blood remains to be elucidated. The present study was undertaken to investigate whether big ET-1 was converted to ET-1 in human blood. In the first experiment, normal serum with synthetic big ET-1 exogenously added or serum from patients with chronic renal failure was incubated in vitro at 37 degrees C for 1 h. In the second experiment, synthetic big ET-1 was incubated in the whole blood at 37 degrees C for 1 h. In the third experiment, synthetic big ET-1 was administered intravenously in anesthetized rat and a plasma sample was obtained before and after 15 min and 1 h. After respective incubation, molecular forms of ET were determined by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassay. There was no significant conversion of big ET-1 to ET-1 in the serum obtained from normal and CRF patients. However, there was a slight but significant increase of ET-1 after incubation of big ET-1 in the whole blood or after administration of big ET-1 in anesthetized rat. The conversion in the whole blood was inhibited by 5 mM EDTA. These results suggest that circulating blood may not be a major site of molecular conversion from big ET-1 to ET-1, although conversion does occur in the circulation by blood cell-mediated process.
Watanabe
Y
Y
Mitsubishiyuka Bioclinical Laboratories, Tokyo Women's Medical College, Japan.
Naruse
M
M
Monzen
C
C
Naruse
K
K
Ohsumi
K
K
Horiuchi
J
J
Yoshihara
I
I
Kato
Y
Y
Nakamura
N
N
Kato
M
M
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019332:Endothelin-1; D016232:Endothelins / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011498:Protein Precursors / Q000097:blood*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors