Regulation Of Pancreatic Enzyme Secretion Research Articles

Digestion and blood biochemical values of hens fed on the diets supplemented with exogenous protease

The paper presents the results of feeding crossbred laying hens of Hisex White breed, one year of age, suffering from chronic fistulae of the main pancreatic duct, on the wheat-soya diet supplemented with exogenous protease. The scope of the study covered the effect of enzymatic preparation Axtra Pro® on exocrine pancreatic function of hens, diet nutrients digestibility, digestive enzyme activity and blood biochemical values. Enzymatic activity of1 gof preparation Axtra Pro® amounted to 897 ± 47.5 mg of casein split during 1 minute (mg/(ml per min), which is 77.6% higher compared to preparation Pancreatine. Supplementing feed with the preparation Axtra Pro® (100g/t of feed) did not affect the amount of pancreatic juice, there were no changes in secretory enzymatic activity. The analysis of postprandial enzyme secretion dynamics made it possible to conclude that when laying hens were fed on the wheat-soya diet supplemented with exogenous protease, there was a decrease in proteolytic activity of the pancreatic juice during the first 60 min after the feed intake. After 150 min, i.e. during the neurohumoral phase of the regulation of pancreatic enzyme secretion, there was a rise in proteolytic activity. At the same time protease activity did not undergo insignificant changes during the experiment; digestibility of protein increased by 1.2% compared to the control group. Supplementing diet with the preparation Axtra Pro® (100 g/t of feed) led to the decrease in the activity of alkaline phosphatase in hens’ blood plasma by 47.8%, and glucose concentration by 9.2% compared to the control group, which proves a positive effect of the preparation on the function of digestive glands.

Immunohistochemical analysis of cholecystokinin A receptor distribution in the rat pancreas

Cholecystokinin (CCK) plays a major role in the regulation of pancreatic enzyme secretion based on its binding to the CCK-A receptor (CCK-AR). While CCK-AR is known to be expressed in rat islet B cells, the localization of CCK-AR in rat pancreatic A and D cells remains poorly understood. The aim of this study was to identify the localization of CCK-AR in rat pancreatic islets by means of double immunofluorescence straining with antibodies against CCK-AR, glucagon, insulin and somatostatin and with in situ hybridization to detect its transcript. CCK-AR-like immunoreactive cells were found to overlap both with glucagon-like immunoreactive cells and insulin-like immunoreactive cells but not with somatostatin-like immunoreactive cells. An in situ hybridization study using a cRNA probe for CCK-AR revealed that CCK-AR mRNA was expressed in the center and periphery of the pancreatic islets. Further to this, immunofluorecsence staining using anti-glucagon antibody was carried out after in situ hybridization using the CCK-AR cRNA probe in order to identify CCK-AR mRNA expressing cells. CCK-AR mRNA exhibited a distribution pattern almost identical to that of glucagon-like immunoreactive cells. These results show clearly that CCK-AR exists not only in B but also in A cells of the rat pancreas, suggesting that CCK regulates the secretion of insulin and glucagon at least partly via CCK-AR.

Inhibitory Effect of the Lectin Wheat Germ Agglutinin on the Binding of 125I-CCK-8s to the CCK-A and -B Receptors of AR42J Cells

Cholecystokinin (CCK) is a peptide hormone and plays a major role both in the regulation of pancreatic enzyme secretion and growth of the gastrointestinal tract. The pancreatic CCK receptors are highly glycosylated membrane proteins that are able to bind plant lectins such as wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA-I). In preceding papers, we demonstrated an inhibition of CCK-8s induced Ca2+ signaling and secretion of rat pancreatic acini and AR42J cells by the lectins WGA and UEA-I (Pancreas 2001;23:368-374). Here we studied the influence of WGA, UEA-I, and 22 other lectins on 125I-CCK-8s binding on AR42J cells. A binding assay was used with 125I-CCK-8s and dexamethasone-stimulated AR42J cells, bearing CCK-A as well as CCK-B receptors. WGA inhibits 125I-CCK-8s binding in a dose-dependent manner. The binding is affected at concentrations of WGA >1 microg/mL. The EC50 for inhibition is 8 microg/mL. At a concentration of 25 microg/mL, WGA inhibits the hormone binding 70%. This inhibition can be abolished by the specific sugars for WGA N,N',N"-triacetylchitotriose and N-acetylglucosamine, but not by N-acetylneuraminic acid. UEA-I diminished hormone binding but without significance, although UEA-I binds to the fucose residues of receptor glycosylations. All other 22 lectins tested here were ineffective. The blockage of CCK receptors by WGA explains the inhibition of CCK-8s induced Ca2+ signaling and the secretion of pancreatic acinar cells and AR42J cells. Although the inhibitory effect of WGA is in agreement with the findings of Santer et al, the results with UEA-I are in contrast to those of Santer et al (1990), who described a strong increase in 125I-CCK-8s binding to isolated crude rat pancreatic cell membranes in the presence of UEA-I.

Role of prostaglandins in regulation of pancreatic enzyme secretion by various diets.

We have demonstrated by the use of isolated rat pancreatic acini that exogenous prostaglandins of the E type inhibit secretagogue-stimulated amylase secretion. We here studied whether the pancreas is a source of prostaglandin synthesis and whether prostaglandins mediate regulation of pancreatic enzyme secretion by various diets. Prostaglandin E2 was measured by enzyme immunoassay in pancreatic acini from either normal animals or after 10 days of feeding with different diets. Acini were prepared by collagenase digestion. Amylase secretion was measured after stimulation with cholecystokinin in the presence or absence of indomethacin, an inhibitor of prostaglandin synthesis. Prostaglandin E2 concentration in pancreatic acini was comparable to other organs such as kidney and liver. Feeding a diet enriched in proteins caused an increase of cholecystokinin-stimulated maximal amylase secretion and a decrease of prostaglandin E2 concentration. Incubation of acini with indomethacin caused a decrease in prostaglandin E2 concentration and an increase in cholecystokinin stimulated amylase secretion. We conclude that regulation of pancreatic enzyme secretion by diets may be mediated by prostaglandins.

Development of Cholecystokinin and Pancreatic Polypeptide Endocrine Systems during the Larval Stage of Japanese Flounder, Paralichthys olivaceus

To understand the developmental process of the endocrine system, which controls the pancreatic exocrine function in Japanese flounder, Paralichthys olivaceus, the expression patterns of cholecystokinin (CCK) and pancreatic polypeptide (PP) during the larval stage were analyzed by immunohistochemistry and in situ hybridization. Expression of CCK in the intestinal epithelia started at 2 days posthatching (dph), 1 day prior to the first feeding. Endocrine pancreatic cells containing insulin were present in the pancreas primodium at hatching, and these endocrine cells formed an islet at 3 dph and developed into the principle islet neighboring gallbladder at 20 dph. However, PP cells were not contained in the principle islet even after metamorphosis. PP cells were contained in the accessory islets differentiated around the proximal part of the pyloric appendages at 30 dph (early metamorphosis stage). Therefore, we infer that the stimulative regulation of pancreatic enzyme secretion by CCK starts to function at the first feeding, whereas the restrictive regulation by PP develops about 1 month later in flounder larvae. In addition, we observed that CCK immunoreactive cells appeared in the accessory islets at 30 dph, similar to PP cells, even though CCK mRNA expression could not be detected in cells from the islets. This indicates the possibility that a peptide that is cross-reacted with the CCK antibody, i.e., gastrin, is synthesized in the flounder islets.

PALLIATION OF PAIN IN CHRONIC PANCREATITIS: Use of Enzymes

According to the concept of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. The author, however, has demonstrated in healthy volunteers that intraduodenal application of porcine pancreatic extracts does not inhibit but rather stimulates pancreatic enzyme secretion. This is probably because of the high-protein content of porcine pancreatic extracts that may overwhelm a potential inhibitory effect of proteases. In a prospective placebo-controlled, double-blind multicenter study to investigate the effect of acid-protected porcine pancreatic extracts on pain in 43 patients with chronic pancreatitis, pain improved in most patients regardless of whether they started with placebo or verum. There was no significant difference between both treatment arms. In a meta-analysis, which included the author's study, six randomized, double-blind, placebo-controlled studies were evaluated. Statistical analysis demonstrated no benefit of the application of porcine pancreatic extracts to relieve pain in chronic pancreatitis. The author concluded that pancreatic extracts neither inhibit pancreatic enzyme secretion nor are they efficient in lowering pain in chronic pancreatitis.

Adaptation of the human pancreas to inhibition of luminal proteolytic activity

Background & Aims: Feedback regulation of pancreatic enzyme secretion is well established in animals, and their pancreases are able to adapt to intraduodenal inhibition of pancreatic enzymes by proteinase inhibitors such as Camostate (FOY-305; Schwarz GmbH, Monheim, Germany). In this study, we addressed whether similar adaptive changes occur in the human pancreas after 4 weeks of 2 g/day Camostate application. Methods: Before, at the end of, and 2 weeks after 4-week Camostate treatment (four times 500 mg daily), pancreatic changes were analyzed with the use of a secretin-cerulein test, a test-meal stimulation, cholecystokinin plasma measurement, and standardized ultrasonographic investigations of the pancreas. Results: Duodenal trypsin output after secretion stimulation was significantly increased (+44%; P < 0.01) and duodenal bicarbonate output decreased 22% ( P < 0.05) after 4 weeks of Camostate application. The size of the pancreatic head (vertical) increased 8% ( P < 0.05) at week 4 and decreased to pretreatment values 2 weeks after treatment (week 6). The other three diameters measured (head oblique, body, and tail) showed a similar pattern. Stimulated cholecystokinin plasma levels 15 minutes after application of a standard test meal increased 62% ( P < 0.05). Conclusions: The human pancreas adapts to oral application of the proteinase inhibitor Camostate. These findings support the theory that feedback control of the exocrine pancreas operates in humans. GASTROENTEROLOGY 1998;115:388-396

Agonists and Antagonists of Regulatory Peptides as Tools to Study Regulation of Pancreatic Exocrine Secretion, Cell Proliferation and Gene Expression

For more than two decades, our research group has been studying the pancreatic actions of three groups of regulatory peptides: members of the cholecystokinin/gastrin family, bombesin-like peptides and somatostatin. Investigating these peptides, our work has focused on three particularly interesting aspects: peptidergic regulation of pancreatic enzyme secretion and growth in adult rats, peptidergic control of pancreatic enzyme secretion and growth during postnatal development in rats, and peptidergic regulation of proliferation and differential gene expression in pancreatic adenocarcinoma cells. Our data confirmed that the control of the exocrine function of the pancreas is complex, and that it involves peptides such as the cholecystokinin/gastrin-like peptides, bombesin-like peptides and somatostatin. In these investigations, it became evident that selective peptide receptor agonists, antagonists and monoclonal antibodies raised against peptides are useful tools to identify the role of these bioactive peptides in pancreatic exocrine secretion and cell proliferation.

Secretory response of cultured acinar cells of rat pancreas to cholecystokinin

To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acinar response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.

Somatostatin inhibits CCK release by inhibiting secretion and action of CCK-releasing peptide.

We hypothesized that somatostatin exerts its inhibitory action on cholecystokinin (CCK) release and pancreatic secretion by inhibiting the secretion and/or action of a CCK-releasing peptide (CCK-RP) secreted from the small intestine. Our studies demonstrated that intravenous infusion of somatostatin (25 micrograms.kg-1.h-1) completely inhibited the increase in amylase output evoked by diversion of bile-pancreatic juice and 80 +/- 10% of the increase in plasma CCK. Intraduodenal administration of concentrated intestinal perfusate containing the CCK-RP collected from a donor rat with bile-pancreatic juice diversion raised amylase output by 2.3-fold and elevated plasma CCK levels to 7 +/- 0.8 pM in a recipient rat. The stimulatory effect of the concentrated intestinal washings was abolished when the "donor" rat was pretreated with somatostatin. In addition, in somatostatin-treated "recipient" rats, intraduodenal administration of intestinal washings containing CCK-RP also failed to elicit an increase in plasma CCK and amylase secretion. Furthermore, using duodenal mucosal explants, we demonstrated that the inhibitory action of somatostatin on CCK release evoked by CCK-RP was antagonized by pretreatment with pertussis toxin. These observations strongly suggest that somatostatin inhibits feedback regulation of pancreatic enzyme secretion by inhibiting both the secretion and action of CCK-RP.

Role of intraluminal nutrients in feedback regulation of pancreatic enzyme secretion.

Role of intraluminal nutrients in feedback regulation of pancreatic enzyme secretion.

Is There a Place for Pancreatic Enzymes in the Treatment of Pain in Chronic Pancreatitis?

According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. However, we have demonstrated in healthy volunteers that intraduodenal application of porcine pancreatic extracts does not inhibit but rather stimulates pancreatic enzyme secretion. This is probably due to the high protein content of porcine pancreatic extracts which may overwhelm a potential inhibitory effect of proteases. In a prospective placebo-controlled, double-blind, multicenter study to investigate the effect of acid-protected porcine pancreatic extracts on pain in 43 patients with chronic pancreatitis, pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between the two treatment arms. The pancreatic extract that we have used in our study neither inhibits pancreatic enzyme secretion nor is it very efficient in lowering pain in chronic pancreatitis.

Treatment of Pain with Pancreatic Extracts in Chronic Pancreatitis: Results of a Prospective Placebo-Controlled Multicenter Trial

According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain.

Feedback regulation of pancreatic exocrine secretion in animal and man

This chapter focuses on studies dealing with the feedback mechanism of pancreatic exocrine secretion in animal and man. Clear evidence is presented that this feedback mechanism is working in the rat and the pig and that this feedback is mediated in the rat by the gastrointestinal hormones pancreozymin (enzyme secretion) and secretin (volume and bicarbonate secretion). Two novel peptides have been described--the 'CCK-releasing peptide' originating from the small intestinal mucosa, and the 'monitor peptide' cosecreted together with the enzymes in the pancreatic juice--to account for the stimulation of pancreatic enzyme secretion by the release of CCK. A similar feedback regulation of pancreatic secretion is working in man. It remains as yet controversial whether the feedback in humans is regulated via hormonal or neural pathways. It is also a matter of debate whether this feedback regulation of pancreatic enzyme secretion could be utilized for therapeutic aims in the treatment of pain in patients with chronic pancreatitis.

Role of Cholecystokinin in the Regulation of Pancreatic Enzyme Secretion in the Rat

Whereas pancreatic exocrine secretion in the rat varies considerably depending on the condition under which a study is performed, it is of great importance to study pancreatic pathophysiology in vivo, while the rat is conscious. In recent years several studies were performed in the conscious rat with a cannulated pancreatic duct, and much progress was made in delineating the role of cholecystokinin (CCK) in the regulation of pancreatic enzyme secretion in more detail. This progress was mainly due to the development of specific and sensitive radioimmunoassays for CCK and the availability of specific CCK-receptor antagonists. In the rat it was shown that a negative feedback regulation mechanism of pancreatic enzyme and CCK secretion exists in which intraluminal trypsin and, to a lesser extent, bile acids and plasma CCK, plasma secretin, and the cholinergic system play important roles. Probably by interference with this feedback mechanism in the rat, casein is a stronger stimulant of plasma CCK release and pancreatic exocrine secretion than fat. Finally, CCK does not play an important role in bombesin-stimulated pancreatic enzyme secretion in the rat.

Regulation of Pancreatic Enzyme Secretion in Conscious Rats by Intraluminal Somatostatin: Mechanism of Action*

These studies were undertaken to characterize 1) the immunoreactive somatostatin (SS) forms found in the gastrointestinal lumen and 2) to assess the possible role of luminal SS on pancreatic exocrine function. Results indicate that different forms of SS are secreted into the rat gastric and duodenal lumen in proportions corresponding to their gastric and duodenal contents. Inhibition of diversion-stimulated pancreatic exocrine secretion by intraduodenal infusion of SS (SS-ID) is dose dependent with a maximal effective dose of 24 micrograms/kg-1h-1 for volume and 48 micrograms/kg-1h-1 for protein output. Infusion of supramaximal doses result in a loss of the inhibitory effect of SS-ID on both volume and protein outputs. Comparison between inhibition of pancreatic secretion by iv SS (SS-IV) and SS-ID indicates that SS-ID is about 20 times less potent than SS-IV in its inhibition of stimulated pancreatic exocrine secretion. Intraileal (SS-IL) infusion of SS at 48 micrograms/kg-1h-1 did not inhibit stimulated pancreatic secretion but was rather stimulatory possibly through the inhibition of putative ileal inhibitors. Likewise, passive immunization against circulating SS did not affect the inhibitory effects of SS-ID on pancreatic secretion. These data indicate that SS is secreted into the rat gastrointestinal lumen and that its infusion into the duodenal lumen inhibits stimulated pancreatic secretion in a dose-dependent fashion. The observation that SS-IL did not inhibit pancreatic secretion and that passive immunization against circulating SS did not affect the inhibitory effect of SS-ID suggest that the action of SS-ID on stimulated exocrine pancreatic secretion is probably indirect and may involve a duodenal signal, possibly an inhibition of endogenous release of cholecystokinin and/or secretin.

Two hypotheses on the feedback regulation of pancreatic enzyme secretion.

We review the mechanisms underlying the feedback regulation of pancreatic enzyme secretion in response to a meal. Pancreatic enzyme secretion in the rat and pig is known to be regulated by a negative feedback mechanism mediated by intestinal trypsin and chymotrypsin. Such a mechanism has recently been noted in humans. The presence of these enzymes in the small intestine suppresses pancreatic enzyme secretion, whereas their removal increases it. Two novel peptides have been proposed to account for the stimulation of pancreatic enzyme secretion in response to feeding trypsin inhibitor. One was assumed to be present in rat pancreatic juice and the other to be spontaneously secreted from the rat small intestine. In either case, trypsin and trypsin inhibitors do not directly interact with the luminal surface of the small intestine, but their actions are mediated by a trypsin-sensitive, cholecystokinin-releasing peptide. This is a novel explanation of the well-recognized stimulation of pancreatic enzyme secretion in response to dietary protein intake.

A cholecystokinin releasing peptide mediates feedback regulation of pancreatic secretion

Diversion of bile pancreatic juice from the duodenum in rats stimulates cholecystokinin (CCK) release and pancreatic enzyme secretion. Intraduodenal perfusion of trypsin inhibits the release of CCK and pancreatic enzyme secretion. We hypothesized that the increased pancreatic enzyme secretion after pancreatic juice diversion is mediated by a trypsin-sensitive peptide secreted by the small intestine that stimulates release of CCK. To test this hypothesis, rats were surgically prepared with bile-pancreatic cannula and intestinal fistulas. Diversion of bile-pancreatic juice stimulated amylase output fivefold above basal and increased plasma CCK from a basal of 0.5 +/- 0.05 pM to 14 +/- 5 pM. Rapid perfusion (3 ml/min) of the duodenum with phosphate-buffered saline reversed the increase in amylase output and lowered the plasma CCK to 1.2 +/- 0.2. Administration of intestinal perfusate (3 ml/min) collected from a donor rat into the duodenum of a recipient rat with diversion of bile pancreatic juice increased amylase output threefold above basal and increased plasma CCK. The stimulatory activity of the intestinal perfusate was inactivated by treatment with trypsin but not by amylase or lipase. In addition, boiling did not alter the stimulatory activity of the intestinal perfusate. Perfusion of intestinal perfusate from donor rats pretreated with atropine did not stimulate amylase output and CCK release in recipient rats. By use of molecular membrane exclusion filters, stimulatory activity was retained (between 1,000 and 5,000). These results indicate that feedback regulation of pancreatic enzyme secretion is mediated by a CCK releasing peptide whose secretion from the duodenum is cholinergically mediated. This peptide is trypsin sensitive and has a molecular weight between 1,000 and 5,000.

Effect of dopamine on amylase secretion from guinea pig pancreatic acinar cells in vitro

Dopamine has been shown to effect pancreatic flow, protein output and amylase secretion in a variety of species. However, there is conflicting evidence regarding the role of dopamine on amylase release in vitro. Specific studies were conducted to evaluate the effect of dopamine and to compare its effects with other substances on basal- and secretagogue-stimulated amylase secretion in a guinea pig dispersed pancreatic acinar cells preparation. Dopamine (10(-6) M) induced a small, but significant (P less than 0.05) increase of amylase secretion. Established secretagogues (10(-6) M) including bombesin, cholecystokinin-octapeptide (CCK-8) and carbachol as anticipated induced significantly larger responses. Other substances tested (10(-6) M) including thyrotropin-releasing hormone (TRH) and muscimol were without effect. Complete dose-response studies (10(-11)-10(-3) M) in the presence of bombesin, CCK-8 and carbachol revealed that dopamine does not affect amylase release in response to these secretagogues. These findings suggest that dopamine is a weak stimulant of amylase secretion in vitro, and that it may therefore play a minor role in regulation of pancreatic enzyme secretion. Several factors including vascular, hormonal and neural have been implicated in regulation of pancreatic exocrine secretion. In particular, autonomic nervous system activity, notably cholinergic, has been shown to affect the secretory status of the pancreatic acinar cell. In addition, several biologically active peptides including bombesin, cholecystokinin (CCK), secretin, vasoactive intestinal peptide (VIP), substance P, gastrin and stimulation of cholinergic (muscarinic) receptors with carbachol have been shown to stimulate pancreatic enzyme secretion both in vivo and in vitro. Certain controversy regarding the role of the sympathetic nervous system in regulation of pancreatic exocrine secretion does exist. For example, several studies with agonists and antagonists of noradrenergic and dopaminergic receptor subtypes suggest a stimulatory effect on pancreatic fluid, electrolyte and enzyme secretion. However, these responses are species-specific and variations inherent to the model have been described. Dopamine administration has been shown to stimulate pancreatic bicarbonate and enzyme secretion in a variety of species including mice, dogs, and man. Radioligand binding studies with 3H-dopamine have revealed the presence of high- and low-affinity dopamine binding sites in dog pancreatic acinar cells. Stimulation of these receptors has been correlated with dose-dependent increases in intracellular cAMP levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Trypsin content in intestines of herring larvae, Clupea harengus, ingesting inert polystyrene spheres or live crustacea prey

In 1986, at the Danish Institute of Fisheries and Marine Research, Denmark, Clupea harengus L. larvae from three different herring stocks were offered either non-biodegradable polystyrene spheres, nauplii and copepodites of Acartia tonsa or Artemia ssp. nauplii. Ingestion of polystyrene spheres induced trypsin secretion to a higher level than in non-feeding fish. Larvae ingesting live food of the same width as the polystyrene spheres exhibited the highest trypsin content in the intestines. Mechanisms responsible for the regulation of pancreatic enzyme secretion are discussed.