Time dependent stimulating effect of glucagon on the capacity of urea-N synthesis in rats.
The effect of glucagon on the capacity of urea-N synthesis was examined in 24 rats as a function of time. First, the conditions for saturation of urea synthesis under glucagon influence were studied by the kinetics of urea-N synthesis rate in relation to arterial blood alpha-amino-N concentration between 5 and 17 mmol/l in 21 nephrectomized rats given zinc-glucagon (20 micrograms s.c. per day) for 14 days. Alanine was infused so that steady state concentrations of total alpha-amino-N was attained in each rat. The urea-N synthesis rate was calculated as accumulation in total body water corrected for intestinal hydrolysis. The relationship suggested a barrier limited substrate inhibition kinetics, as earlier found in control rats, and data were examined accordingly by non-linear regression analysis. The estimated kinetic constants were: Vmax = 71 mumol/(min X 100 g body wt), Km = 5.4 mmol/l, Ki = 2.4 mmol/l, and the barrier = 4.4 mmol/l. Vmax was increased three times compared with controls. The capacity of urea-N synthesis, i.e. the zenith of the relation, was attained in the concentration interval 7.5 to 12.0 mmol/l, as in controls. The capacity of urea-N synthesis was determined during i.v. infusion of zinc-glucagon (0.15 microgram per min) and after 2, 8, and 14 days of daily s.c. injections of 20 micrograms zinc-glucagon. Rats given zinc-protamine solution were controls.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004338:Drug Combinations / Q000008:administration & dosage; D005260:Female; D005934:Glucagon / Q000008:administration & dosage*; D007700:Kinetics; D009584:Nitrogen / Q000378:metabolism; D011479:Protamines / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014508:Urea / Q000096:biosynthesis*
D004338:Drug Combinations; D011479:Protamines; C047696:glucagon, protamine zinc-; D014508:Urea; D005934:Glucagon; D009584:Nitrogen