Ornithine decarboxylase along the mouse and rat nephron.
Renal arginase activity is a potent source of ornithine (Orn) for polyamine synthesis. Ornithine decarboxylase (ODC) was localized along the mouse and rat nephron by incubating viable nephron segments isolated by microdissection from collagenase-treated kidneys with or without D,L-2-(difluoromethyl)ornithine (DFMO), a selective inactivator of ODC. Tubules from either control or DFMO-treated animals were incubated with 100 ¿M L-[1-14C]Orn. In control mice, Orn decarboxylation occurred mainly in the proximal convoluted tubule (PCT). In DFMO-treated mice, Orn decarboxylation was dramatically reduced in PCT and in proximal straight tubules (PST). In rats, Orn decarboxylation also occurred predominantly in the proximal tubule. Addition of 10 mM DFMO to isolated tubules dramatically decreased Orn decarboxylation in PCT and in PST. Thereafter, ODC activity was demonstrated in permeabilized tubules. In Triton X-100-treated tubules from control mice, ODC was exclusively found in proximal tubules (PCT > PST). This ODC activity was strongly inhibited in DFMO-treated mice. In conclusion, the highest ODC activity was found in rat and mouse PCT, a segment devoid of arginase. We hypothesize that the filtered Orn, which is reabsorbed along the PCT,is the main source of Orn for ODC.
Levillain
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O
Laboratoire de Physiopathologie Métabolique et Rénale, Faculté de Médecine Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM), Lyon, France. levillai@cimac-res.univ-lyon1.fr
Hus-Citharel
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A
D000818:Animals; D001119:Arginase / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D003653:Decarboxylation; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000201:enzymology; D008297:Male; D051379:Mice; D009399:Nephrons / Q000201:enzymology*; D009952:Ornithine / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D002245:Carbon Dioxide; D009952:Ornithine; D001119:Arginase; D009955:Ornithine Decarboxylase; D000518:Eflornithine