Chymodenin, a duodenal peptide: specific stimulation of chymotrypsinogen secretion

Abstract

Chymodenin, a basic porcine duodenal peptide, was administered to anesthetized rabbits intravenously or added to the medium bathing the isolated pancreas. In the 10(-8)M range, chymodenin rapidly increased chymotrypsinogen (ChTg) secretion, did not increase lipase secretion, and modestly enhanced protein secretion (which could be attributed primarily to augmented ChTg secretion). The increased ChTg output was too rapid to be the result of increased rates of protein synthesis and could not be attributed to the exocytosis os zymogen granule contents because of the enzyme-;pecific nature of the response. In contrast to shymodenin, cholinergic stimulation in vitro produced a relatively lipase-rich, chymotrypsinogen-poor secretion. Lipase and ChTg outputs, which varied relatively independently under unstimulated conditions, covaried in the presence of chymodenin. The existence of a duodenal peptide that produces an enzyme-specific response supports the hypothesis that the secretion of digestive enzymes during digestion is a highly regulated process in which the enzyme content of pancreatic secretion varies with differences in the composition of intestinal substrates.

Absence of Rapid Adaptation of the Exocrine Pancreas of Conscious Dogs to Diets Enriched in Fat or Carbohydrates

“…Besides, most of the experiments that have demonstrated adaptation of the exocrine pancreas to the diet, have mainly been done in anaesthetized animal (LaBella et al, 1981;Tseng et al, 1982) in perfused organs or in vitro preparations of the gland (Rothman, 1967(Rothman, , 1976Adelson & Rothman, 1975;Palade, 1975;Rothman & Wilking, 1978;Dagorn, 1979) whereas experiments in conscious animals, under nearly physiological conditions, are scarce.…”

Compartmentalization of Pancreatic Secretory Zymogen Granules as Revealed by Low-Voltage Transmission Electron Microscopy

“…Indeed, Rothman as well as others have shown that secretion of pancreatic enzymes can occur in a non-parallel fashion, so that the nature of the pancreatic juice does not correspond to a homogeneous mixture of all pancreatic enzymes. Selective discharge of certain proteins does occur under particular conditions of stimulated secretion (Adelson and Rothman 1975;Rothman 1976Rothman , 1981Dagorn, 1978;Adelson and Miller 1985;Sommer et al 1985;Rothman et al, 1991;de Dios et al 1999). On the other hand, Anderson, Jena, and colleagues (Anderson 2004;Jena 2004Jena , 2009) have introduced the concept of a discharge mechanism different from the classical exocytotic event (in which the entire granule fuses in one single event with the plasma membrane).…”

Rapid Adaptation of Pancreatic Enzyme Secretion in the Conscious Rat

“…Furthermore, it was postulated that this change in composition of secreted en zymes is specific to the diet fed, e.g. that dur ing digestion of a carbohydrate meal, the secretion of amylase is much more pro nounced than that of other enzymes [7,32], An increasing number of studies attempt to confirm or to disprove these findings using in vitro rabbit pancreas [1,26,27,30,31], guinea pig pancreatic lobules [22], anesthe tized or conscious rats [4-7, 9, 11, 17, 32], Even when independent groups used appar ently the same experimental protocol, differ ent results were obtained [9,11,17,26,27,30,31]. Remarkably few experiments have been done in conscious rats [4,5] compared to the numerous in vitro techniques.…”

“…It was substituted by an equivalent amount of prccollected juice. Thereafter, the secretion rate was stimulated for at least I h by several different meth ods: (1) h; n = 9); (3) intraduodenal infusion of a amino acid mixture (Aminopaed®; n = 8); (4) intraduodenal infu sion of a lipid mixture (Intralipid®, 10%; n = 8); (5) in traduodenal infusion of 10% sucrose (n = 8). In con trol experiments the basal pancreatic secretion rate was studied under complete recirculation of the juice or under intraduodenal or intravenous infusion of 0.9% NaCl.…”

“…That would mean that stored enzymes were released in response to the diet actually fed, i.e., amylase is preferen tially secreted when starch-rich food reaches the duodenum. This rapid adaptation or 'nonparallel secretion' was also found after application of different secretagogues [26,27], These latter experiments have mainly been done in anesthetized animals [17,32], in perfused organs or in vitro preparations of the gland [1,6,19,24,26,27], whereas experiments in conscious rats are scarce [4,5], For this reason the problem was reinvesti gated in an in vivo model using conscious rats under nearly 'physiological' conditions.…”