Diuretic and natriuretic effect of ebelactone B in anesthetized rats by inhibition of a urinary carboxypeptidase Y-like kininase.
Ebelactone B (EB) (10(-7)-10(-5) M) inhibited dose-dependently carboxypeptidase (CP) Y-like exopeptidase, one of the major kininases separated from rat urine, whereas it inhibited neither CPA, CPB or neutral endopeptidase (NEP). Degradation of bradykinin (BK) to BK-(1-8) in rat urine was completely inhibited by EB (10(-5) M) with the increased generation of BK-(1-7). Intraduodenal administration of EB (3 mg/kg) to anesthetized rats caused marked diuresis (by 110%) and natriuresis (130%), in parallel with the increase in urinary kinin levels (110%). Intravenous infusion of a BK antagonist, Hoe140 (3 mg/kg/hr), strongly blocked both EB-induced diuresis and natriuresis. EB may be a novel type of diuretic and natriuretic agent that acts by increasing urinary kinin levels.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Kuribayashi
Y
Y
Ikeda
Y
Y
Adachi
K
K
Kato
H
H
Katori
M
M
Aoyagi
T
T
D000595:Amino Acid Sequence; D000758:Anesthesia; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000652:urine*; D004231:Diuresis / Q000187:drug effects*; D010450:Endopeptidases / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D007783:Lactones; C030795:ebelactone B; C065679:icatibant; D002268:Carboxypeptidases; D010450:Endopeptidases; C022633:serine carboxypeptidase; D001920:Bradykinin