SUMMARY Studies of gastrin metabolism were performed in four dogs before and after nephrectomy. Synthetic human gastrin I was infused for two hours and serum samples were obtained at various times during and after infusion. Serum concentrations of gastrin were measured by radioimmunoassay. A two-compartment model was employed to calculate half-lives under each of four experimental conditions, low and high infusion rates, used both before and after nephrectomy. The model half-life was greatly prolonged after nephrectomy at both infusion rates (from 2.54 min to 5.15 min at the low rate, and from 2.85 min to 7.88 min at the high rate). The metabolic clearance rate, an expression of the rate of catabolism during infusion, decreased significantly after nephrectomy at both infusion rates. These observations indicate that the kidney is an important organ for the catabolism of exogenous gastrin.Synthetic human gastrin I has been shown to have a short half-life when it is infused into dogs (Reeder, Jackson, Brandt, and Thompson, 1972b). This is in accordance with the brief physiological action that infusions of gastrin II have in man (Makhlouf, McManus, and Card, 1966).Evidence has been presented that in dogs synthetic human gastrin may be inactivated in vivo by the kidney (Clendinnen, Davidson, Reeder, Jackson, and Thompson, 1969) and the liver (Thompson, Reeder, Davidson, Charters, Bruckner, Lemmi, and Miller, 1969), and in vitro by the lung, skeletal muscle, and gastric fundus mucosa (Thompson, Reeder, Davidson, Jackson, and Clendinnen, in press). Of these sites the kidney is believed to be the most efficient (Clendinnen et al, 1969).The effect of nephrectomy on the half-life of circulating exogenous gastrin in dogs has been determined by measuring the rate of disappearance
MethodSynthetic human gastrin I was infused in four healthy, alert mongrel dogs weighing 17-22 kg. A catheter for infusion was placed in the superior vena cava and a catheter for sampling was inserted in the iliac vein. Synthetic human gastrin I was given to the fasting dogs according to two dosage regimens. The low dose consisted of a loading injection of 4 micrograms (pg), followed immediately by infusion at the rate of400 nanograms (ng)/kg/hour for two hours. The high dose was 8 ,ug given as a load and 800 ng/kg/hour infused for two hours. These two infusions, given in random order, were separated by a rest period of two days. Infusion of gastrin at these rates resulted in nearly constant values for serum gastrin after one hour. Two basal serum samples for gastrin measurement were obtained before the administration of exogenous gastrin. Additional samples were obtained at the end of the infusion (time zero), and at one, two, three, four, five, eight, 10, 15, 30, and 60 minutes thereafter. One week after the completion of these experiments, both kidneys were removed under general anaesthesia. The dogs were then allowed to recover for two days 462 on 12 May 2018 by guest. Protected by copyright.
