Catabolism of gastrin and secretin

Abstract

In order to determine whether the uptake of gastrin and secretin is limited to specific organ systems (especially the kidney) or whether loss is a nonspecific occurrence across all capillary beds, we have measured the uptake of endogenous and exogenous gastrin and secretin in 32 anesthetized dogs. In 6 dogs, antral irrigation with 0.5% acetylcholine solution produced a brisk increase in gastrin concentrations measured in blood from the aorta. Concentrations in blood from the renal, jugular, and femoral veins were all significantly lower, and there was an integrated uptake of gastrin of 48% by the kidney, 43% by the hind leg, and 36% by the head (the differences were not significant from one another). Exogenous infusion of synthetic human gastrin in 6 dogs at 2 dose levels (0.4μg/kg‐h and 0.8μg/kg‐h) caused a rise in aortic blood concentration of gastrin with significantly lower levels in blood from the renal, femoral, and jugular veins. Calculated as integrated gastrins, the kidney removed 42%, the hind leg 35%, and the head 30% of gastrin at 0.8/μg/kg‐h. Similar percentages were extracted at the lower dose. In 5 dogs, endogenous release of secretin was secured by duodenal irrigation with 0.1 N HCl. This brought about an elevation in the aortic blood concentration of secretin from a basal level of around 60 pg/ml to 217 ±24 pg/ml at 45 minutes. Secretin concentrations in blood from the renal, femoral, and jugular veins were significantly lower, and the kidney removed 39%, the leg 29%, and the head 32% of integrated endogenously released secretin. There was no difference between the 3 sites. During infusion of exogenous secretin at 0.4 U/kg‐h, mean aortic blood levels ranged between 340–420 pg/ml, and levels in the blood from the renal, femoral, and jugular veins ranged between 220–295 pg/ml. When integrated secretin values were determined, the kidney was found to remove 42%, the hind leg 43%, and the head 43%. When secretin was given at 1 U/kg‐h, the kidney removed 46%, the hind leg 31%, and the head 26%. We conclude that extraction of gastrin and secretin occurs on transit of all capillary beds and appears to be a nonspecific process.

Removal of Circulating Gastrin and Cholecystokinin into the Lumen of the Small Intestine

“…Strunz et al [20] and Thompson et al [23] have shown that removal of gastrin upon transit through the vascular beds of the kid ney, intestine, head and hind leg, was about the same in dogs, which suggests that the mechanism of removal is not specific to any one organ. Recently, Peterson et al [16] have shown that gastrin degradation in man is not confined to certain specific organs, but takes place in many organs, or perhaps in the total volume of distribution for gastrin.…”

Hepatic and Intestinal Elimination of Endogenous Gastrin in Pigs

“…Elimination of gastrin has been recorded in kidneys, intestines, hindlimb. and head [8][9][10]. The lack of a significant extraction of amidated and glycineextended gastrin in the gut does not preclude elimination…”

“…Gastrin is produced in antral G-cells by cleavage of progastrin into bioactive peptides of different chain length [1], The peptides undergo various covalent mod ifications including conversion of glycine-extended pro cessing intermediates to carboxyamidated bioactive gas trins [2][3][4], The glycine-extended precursors are released to circulation together with the active carboxyamidated gastrins [5][6][7], Studies in dog and sheep have shown that gastrin is cleared from plasma in several vascular beds [8][9][10], After release from G-cells, gastrin peptides pass the liver to enter the systemic circulation. The role of the liver in gastrin metabolism is, therefore, of considerable interest.…”

Pleiotropic Effects of Secretin: A Potential Drug Candidate in the Treatment of Obesity?

“…Secretin has a relatively short half-life in plasma in humans (2.5-4.0 min) ( 34 – 37 ). Animal studies have revealed that secretin removal from the circulation occurs mainly through the kidneys ( 38 ) but also the capillary beds of various other tissues ( 39 , 40 ). Despite the kidneys being an important organ for secretin removal, only small amounts of secretin appear in the urine ( 41 ) because, after glomerular filtration, secretin is reabsorbed in the distal part of the nephron ( 42 , 43 ).…”