Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

Abstract

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.

Effects of Intraduodenal Administration of HCl and Glucose on Circulating Immunoreactive Secretin and Insulin Concentrations

“…Mean ti of disappearance from peripheral venous serum was found to be 2.8 min. This value is similar to recently reported disappearance rates of the gastrin heptadecapeptide (28)(29). The calculated V averaged 17.4% of the body weight.…”

Disappearance half-time of endogenous and exogenous secretin in dogs.

“…Previous work has shown the metabolic clearance rates to vary with the dose of hormone administered and the serum levels achieved (Clendinnen et al, 1973), but, in the present investigation, secretin levels after infusion of exogenous hormone were higher than after release of endogenous secretin (632 ± 41 pg/ml against 389 ± 56 pg/ml) and the Ti was slightly shorter (2 45 minutes against 2-85 minutes).…”

Serum Gastrin in Chronic Renal Failure: Morphological and Physiological Correlations

“…Secretory functions of the stomach have also been studied [12,18,20,47] and their relation to SG levels have also been documented [14-17, 23, 27, 32, 43, 46. 49, 50], Morphology of the stomach and types of lesions in uremia have also attracted attention [6,7,9,22,24,31,34,36,39,52]. Patients with CRF demonstrate elevated SG levels in the present study.…”