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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 91 records · Page 5Linked to original sources
PubMed1995

Galanin inhibits cholecystokinin secretion in STC-1 cells.

Neuropeptides such as gastrin releasing peptide and pituitary adenylate cyclase activating polypeptide (PACAP) stimulate CCK secretion from CCK producing cells. We hypothesized that in addition to somatostatin, galanin may also play an inhibitory role on CCK secretion. The effect of galanin on CCK secretion was studied in a CCK-producing murine neuroendocrine tumor cell line, STC-1. Galanin below 10 nM did not affect basal CCK secretion but dose- and time-dependently inhibited KCl-stimulated CCK secretion. Galanin also inhibited forskolin-, bombesin- and PACAP- but not dibutyryl cAMP- or beta-TPA-stimulated CCK secretion. The inhibitory effect of galanin was reduced partially by a blocker of ATP-sensitive K+ channel (K+ ATP), glibenclamide, and prevented by pretreatment of the cells with PTX. The results indicated galanin regulates CCK secretion by modulation of K+ ATP and cAMP production through receptors coupled to a PTX-sensitive G protein.

Adenylate Cyclase Toxin↗
PubMed1995

The mechanism of inhibitory action of secretin on gastric acid secretion in conscious rats.

1. Secretin has been recognized as an important enterogastrone. In order to investigate the mechanism of secretin-induced inhibition of gastric acid secretion, the effects of both anti-somatostatin antibody and indomethacin on acid secretion were examined in conscious rats with gastric cannulas. 2. Secretin given intravenously at 5.6 pmol kg-1 h-1 inhibited profoundly the acid secretion stimulated by pentagastrin at 0.3 microgram kg-1 h-1. 3. When a rabbit antisomatostatin serum was given intravenously, it not only abolished the secretin-induced inhibition on the pentagastrin-stimulated acid secretion, but also augmented both basal and pentagastrin-stimulated acid secretion. 4. Indomethacin also significantly augmented basal acid secretion, starting 45 min after the drug delivery began. It reversed the secretin-induced inhibition but it did not augment the pentagastrin-stimulated acid secretion. 5. Neither antisomatostatin serum influenced prostaglandin E2-induced inhibition of the pentagastrin-stimulated acid secretion, nor did indomethacin affect the inhibition by somatostatin, suggesting strongly that the inhibition by somatostatin is not mediated by endogenous prostaglandins, nor is that by prostaglandins E2 mediated by endogenous somatostatin. 6. It is concluded that the inhibitory action of secretin on pentagastrin-stimulated gastric acid secretion is mediated by both somatostatin and prostaglandins in conscious rats. The two inhibitors do not seem to interact endogenously for the inhibition of acid secretion. While endogenous somatostatin exerts a tonic inhibitory effect on both basal and pentagastrin-simulated acid secretion, prostaglandins augment basal acid secretion only.

Animals↗
PubMed1995

Establishment and characterization of TSGH9201, a human gastric carcinoma cell line that is growth inhibited by epidermal growth factor.

A human signet ring gastric carcinoma cell line TSGH9201 was established in vitro. The cells grew in vitro as a monolayer with polygonal morphology and had a population doubling time of 34 hours. The cells secreted tumor markers CEA and CA 125. They were, however, not tumorigenic in athymic nude mice. Karyotypic analysis demonstrated a near tetraploidy with a modal chromosome number of 98. Northern blotting and immunocytochemical analysis revealed the expression of both transforming growth factor alpha and high levels of epidermal growth factor receptor. Cell growth was inhibited by the epidermal growth factor in vitro. The cell line may be a useful tool to study autocrine growth regulation through the epidermal growth factor receptor.

Animals↗
PubMed1995

Effect of streptozotocin-induced diabetes mellitus on release of vasoactive intestinal polypeptide from rodent small intestine.

Representative longitudinal muscle strips (6 x 10 mm) from proximal and distal small intestine were excised from control and streptozotocin-treated rats after one month of untreated and insulin-treated diabetes. Untreated diabetes significantly reduced tissue concentrations of vasoactive intestinal polypeptide (VIP) at both intestinal loci. Insulin treatment of the diabetic animals restored tissue VIP concentrations to control group levels, although the beneficial effect of insulin treatment was only significant in the duodenum. Spontaneous release of VIP was significantly attenuated by untreated diabetes at both intestinal sites. In the duodenum, insulin treatment of the diabetic animals restored VIP release to levels indistinguishable from control group values. In the ileum, insulin treatment produced levels of VIP release that were not significantly different from those of the control and untreated diabetic groups. Tetrodotoxin (5 x 10(-6) M) significantly--but incompletely--inhibited VIP release from control group animals at both intestinal sites. These observations indicate that diabetes mellitus significantly diminishes VIP tissue concentrations and release from intestinal myenteric nerves. These abnormalities improve with insulin treatment. However, the mechanisms of VIP release from proximal and distal intestine appear to differ not only in their response to the diabetic state, but also in their response to insulin treatment.

Animals↗
PubMed1995

Artificial cells with emphasis on bioencapsulation in biotechnology.

The most common use of artificial cells is for bioencapsulation of biologically active materials. Each artificial cell can contain combinations of materials. The permeability, composition and shape of an artificial cell membrane can be varied using different types of synthetic or biological materials. These possible variations in contents and membranes allow for large variations in the properties and functions of artificial cells. Artificial cells containing adsorbents have been a routine form of treatment in hemoperfusion for patients. This includes acute poisoning, high blood aluminum and iron, and supplement to dialysis in kidney failure. Artificial red blood cell substitutes based on modified hemoglobin are already in Phase I and Phase II clinical trials in patients. Artificial cell encapsulated cell cultures are being studied for the treatment of diabetes, liver failure, gene therapy and other conditions. Research on artificial cells containing enzymes includes their use for treatment in hereditary enzyme deficiency diseases and other diseases. Recent demonstration of extensive enterorecirculation of amino acids in the intestine has allowed oral administration to deplete specific amino acids. One example is phenylketonuria, an inborn error or metabolism resulting in high systemic phenylalanine levels. Preliminary clinical studies in patients using bioencapsulation of cells or enzymes have started. Artificial cells containing complex enzyme systems convert wastes like urea and ammonia into essential amino acids. Artificial cells are being used for the production of monoclonal antibodies, interferon and other biotechnological products. Other areas of biotechnological uses include drug delivery, and other areas of biotechnology, chemical engineering and medicine.

Aluminum↗
PubMed1995

Negative feedback regulation of pancreatic exocrine secretion in guinea pigs.

We have investigated whether hormonally mediated negative feedback mechanisms regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea pigs prepared with a tube in the proximal duodenum, pyloric ligation, and pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for as long as 4 h in fasting states failed to increase either pancreatic secretion or plasma levels of secretin or cholecystokinin (CCK). In the same animal preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in significant increases in both pancreatic secretin and plasma levels of the two hormones that were significantly suppressed by ID infusion of pancreatic juice or a combination of trypsin and chymotrypsin. In another group of guinea pigs, this significant increase in pancreatic secretion was profoundly suppressed by a rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a combination of the antiserum and loxiglumide completely abolished the pancreatic secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated pancreatic secretion and hormone release was also studied. Atropine completely suppressed the pancreatic secretion of volume flow, bicarbonate, and protein stimulated by SO, whereas neither one of the two hormone levels was affected by intravenous atropine, indicating that atropine blocks the actions of both secretin and CCK on the pancreatic exocrine secretion. It is concluded that a negative feedback regulation of exocrine pancreatic secretion is operative in the intestinal phase of pancreatic secretion in guinea pigs and that this feedback mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs, cholinergic tone plays an important modulating role in the mechanism.

Animals↗
PubMed1995

Effect of endogenous insulin on pancreatic exocrine secretion in perfused dog pancreas.

Canine pancreas was perfused with an intraarterial infusion of Krebs-Ringer bicarbonate solution containing 5% dog red blood cells, 0.1% bovine serum albumin, and 3% dextran at 15 ml/min, while portal effluent was continuously collected. Pancreatic juice was obtained in 15-min samples via main pancreatic duct cannulation. After a 1-h basal period, secretin and cholecystokinin-8 (CCK), at doses of 2.5 ng.min-1 each, were simultaneously infused for 10 min, with background infusion of a normal rabbit serum (NRS) or an antiinsulin serum (Anti-I) in 5 ml each via a sidearm of the intraarterial catheter. The infusion of secretin and CCK resulted in a significant increase in pancreatic bicarbonate and protein secretion during the infusion of NRS, whereas the pancreatic secretory response of bicarbonate and protein was profoundly suppressed by the infusion of Anti-I in six pancreata so studied. This suppression by Anti-I coincided with significant increases in somatostatin and pancreatic polypeptide levels in portal venous effluent. In three additional pancreata, simultaneous infusions of Anti-I with antisomatostatin (5 ml) and antipancreatic polypeptide (5 ml) serum failed to inhibit the pancreatic exocrine secretion. These results indicate that secretin- and CCK-stimulated pancreatic secretion of bicarbonate and protein depends heavily on local action of insulin. The suppression by Anti-I of pancreatic secretion is mediated, in part, by local releases of somatostatin and pancreatic polypeptide. Thus, the insuloacinar axis plays an important regulatory role in pancreatic exocrine secretion in the dog, and it involves at least three islet hormones including insulin, somatostatin, and pancreatic polypeptide.

Animals↗
PubMed1995

Kinetic analysis of UDP-glucuronosyltransferase in bilirubin conjugation by encapsulated hepatocytes for transplantation into Gunn rats.

Kinetic analysis of the enzyme UDP-glucuronosyltransferase (UDPGT), responsible for the conjugation of bilirubin, suggests that it is a multisubunit enzyme in which there is cooperative binding of the substrate to the subunits. The binding of bilirubin to UDPGT shows positive cooperativity with an apparent Hill coefficient of 2.9. The binding of UDP-glucuronic acid (UDPGA) exhibits kinetics with mixed cooperativity with an apparent Hill coefficient of 4.028. Homogenized rat hepatocytes, intact hepatocytes, and hepatocytes encapsulated in alginate-polylysine-alginate artificial cells, when incubated with bilirubin (1.6 mM) and UDPGA (20 mM), can form monoconjugated and diconjugated bilirubin. However, the presence of the artificial membrane offers some mass transfer resistance. The intraperitoneal transplantation into the Gunn rat of free and microencapsulated Wistar rat hepatocytes shows that both are equally effective in lowering the serum bilirubin. Thus, the membrane did not contribute to a lowering of efficacy after transplantation.

Alginates↗
PubMed1995

Neuronal regulation of the release and action of secretin-releasing peptide and secretin.

The acid-stimulated release of secretin is mediated by a secretin-releasing peptide (SRP) in rats. In the present study we investigated to determine whether a neural mechanism(s) is involved in the regulation of release and action of SRP in anesthetized rats. A concentrated acid perfusate (CAP) containing SRP was obtained from donor rats. CAP administered to recipient rats significantly increased pancreatic flow volume (81.6 +/- 18.3%), bicarbonate output (188.7 +/- 15.6%), and plasma secretin level (from 0.9 +/- 0.2 to 4.4 +/- 0.5 pM). However, this effect was attenuated by CAP from donor rats pretreated with tetrodotoxin (TTX), propranolol, bilateral subdiaphragmatic vagotomy (BSV), or systemic and topical administration of capsaicin. In contrast, CAP from donor rats pretreated with phentolamine, atropine, or hexamethonium did not alter the increase in plasma secretin concentration and pancreatic secretion. Moreover, the action of CAP on secretin release was significantly inhibited in the recipient rats pretreated with TTX, BSV, and topical applications of capsaicin but was not suppressed in the recipient rats pretreated with atropine, hexamethonium, or propranolol. Furthermore, perivagal and duodenojejunal mucosal application of capsaicin abolished the pancreatic secretory response to secretin at 5 pmol.kg-1.h-1. In conclusion, the release and action of both SRP and secretin are mediated by a vagal afferent pathway. beta-Adrenergic receptors also play a significant role in the release of SRP.

Acids↗
PubMed1995

A new theory of enterorecirculation of amino acids and its use for depleting unwanted amino acids using oral enzyme-artificial cells, as in removing phenylalanine in phenylketonuria.

Oral binders remove intestinal bile acid and prevent its reabsorption and recycling thereby lowering systemic cholesterol levels. The results in this paper demonstrate the presence of another extensive enterorecirculation for amino acids. Pancreatic and other glandular secretions into the intestine contain large amounts of proteins, enzymes and polypeptides. Tryptic digestion converts these into amino acids which are then reabsorbed back into the body as they pass down the intestine. This paper shows that this forms a large enterorecirculation of amino acids between the body and intestine. The dietary protein source of amino acids is negligible when compared to the endogenous source, since this paper shows that protein-free diet did not alter the intestinal amino acid concentration. This raises the possibility of using this for the selective depletion of specific body amino acids. In this paper we use a phenylketonuria (PKU) model in rats to test the use of this hypothesis. In PKU rats, artificial cells microencapsulated phenylalanine ammonia lyase (PAL) given orally is more effective than a phenylalanine-free diet. The enzyme artificial cells are more efficient in lowering PHE in the intestine, plasma and cerebrospinal fluid. Compared to PKU on PHE-free diet, this has resulted in better weight gain and general physical condition. Preliminary studies also show that artificial cells microencapsulated asparaginase, glutaminase and tyrosinase given orally can deplete the corresponding amino acid from the intestine.

Amino Acids↗
PubMed1995

Enzyme replacement therapy in ENU2 phenylketonuric mice using oral microencapsulated phenylalanine ammonia-lyase: a preliminary report.

The presence of an extensive enterorecirculation of amino acids between the intestine and the body allows the removal of systemic phenylalanine in PKU rats by oral microencapsulated phenylalanine ammonia lyase. The work presented in this article has the main goal of assessing the feasibility of yeast phenylalanine ammonia-lyase (PAL) loaded collodion microcapsules in reducing elevated plasma phenylalanine concentrations to standard levels in genetically mutated PKU mice, within a 30 day time frame. The distinguishing aspect from previous studies lies in the available animal model. Rather than artificial induction of elevated phenylalanine plasma levels, the mice representing the human phenylketonuric condition, are mutated strains which are deficient in the enzyme phenylalanine hydroxylase. The first in vivo study established a method for orally feeding microcapsules, both control and enzyme loaded, over 30 consecutive days, by mixing with soft, unripened cheese. Under this unique regime a decrease of 51.3% +/- 9.02% in phenylalanine plasma levels was observed after 23 days. Reduction in the phenylalanine plasma levels to within the desired maintenance range of 250-1000 umol/L was observed in 2 out of 4 PAL treated mice, with only 50% of the PAL dose used in previous rat studies by Chang's group. The second animal study confirmed the finding in the first in vivo study that there is no significant decrease in the plasma phenylalanine levels within the first seven days. This may be due to the severely deteriorated physical condition of the ENU mice used, the PAL enzyme preparations available or the fact that normal mice contain 10 times the amount of phenylalanine hydroxylase as compared with humans, thus requiring larger doses of PAL in order to be effective in a shorter time span.

Administration, Oral↗
PubMed1995

Superoxide dismutase and catalase cross-linked to polyhemoglobin reduces methemoglobin formation in vitro.

Superoxide dismutase (SOD) and catalase (CAT) were evaluated for their ability to reduce methemoglobin formation in chemically cross-linked hemoglobin that was incubated in Tris-HCl buffer. Two parallel studies were carried out using identical experimental conditions with one exception only. This involved the physical state of SOD and CAT in solution such that the enzymes were either cross-linked directly to hemoglobin (hemoglobin-SOD-CAT) or simply incubated with polyhemoglobin. The concentration of SOD and CAT was subsequently varied to examine and compare the effect on the rate of methemoglobin formation between the two experiments. Overall, a comparison between the results clearly indicated that cross-linking SOD and CAT to hemoglobin was more effective at reducing methemoglobin levels than incubating polyhemoglobin with SOD and CAT. More specifically, the incubation experiment would require an enzyme concentration exceeding twice that cross-linked to hemoglobin in order to achieve a similar beneficial effect. However, it was more striking to observe that the presence of SOD and CAT during the cross-linking reaction had markedly reduced the initial formation of methemoglobin. When SOD and CAT were included during the chemical process of generating polyhemoglobin, about 7% methemoglobin was formed in the cross-linked hemoglobin-SOD-CAT product. By comparison, methemoglobin had increased about 20% after the cross-linking reaction when generating polyhemoglobin.

Animals↗
PubMed1995

Effect of donor strains and age of the recipient in the use of microencapsulated hepatocytes to control hyperbilirubinemia in the Gunn rat.

Hepatocytes of certain rat strains are spontaneously accepted when they are implanted in the peritoneal cavity. Therefore to evaluate if microcapsules are able to immunoisolate the hepatocytes, it is necessary to find the strain of rat whose free hepatocytes are rejected. Hepatocytes were collected from Buffalo rats and were implanted intraperitoneally in one year old Gunn rats. During the first two weeks both groups of Gunn rats which received free and encapsulated hepatocytes showed a reduction in the bilirubin level relative to the control. After 15 days, the bilirubin levels increased in the group which received free hepatocytes. This suggests that an acute rejection had taken place. Bilirubin continued to stay high until the end of the experiment and there was no difference between this group and the control. As the animal ages, there is a significant accumulation of bilirubin in the tissues which affects the net reduction of serum bilirubin since once bilirubin is conjugated by the transplanted hepatocytes and eliminated, some of the bilirubin deposited in the tissues diffuses into the blood preventing a major drop in serum bilirubin levels. The findings that UDP-glucuronosyltransferase (UDPGT) activity of Buffalo rat hepatocytes is the same as the UDPGT activity of Wistar rat hepatocytes, imply that the age of the animal is a very critical factor in determining how great the depression of serum bilirubin will be after implantation of hepatocytes.

Animals↗
PubMed1994

Effect of rate of intracellular transport and diacytosis on cytotoxicity of hybrid toxins. Study with hybrids using hepatic asialoglycoprotein receptor-mediated endocytosis.

The effects of diacytosis and intracellular transport rate on cytotoxicity of hybrid toxins were studied with conjugates of diphtheria toxin fragment A (DTA) to asialoorosomucoid (ASOR) and its reduced and carboxymethylated cyanogen bromide fragment I (RC-ASCNBr-I) in cultured rat hepatocytes. In the hepatocytes the kinetics of uptake of the conjugate of asialoorosomucoid (DTA-ASOR) and that of the conjugate of the cyanogen bromide fragment (DTA-RC-ASCNBr-I) were quite similar, but the rate of accumulation of DTA moiety into the lysosomes, as determined by Percoll density gradient centrifugation, was found to be greater for the latter than the former. However, after internalization, DTA-RC-ASCNBr-I was diacytosed to a lesser extent than that of DTA-ASOR, particularly when colchicine was present during internalization. Analysis of the subunits of DTA-ASOR internalized by the hepatocytes indicated that they were accumulated disproportionately in a time-dependent manner so that the glycoprotein moiety was accumulated progressively more than the toxin moiety. Cytotoxicity of DTA-ASOR toward the hepatocytes was 2-times as much as that of DTA-RC-ASCNBr-I. Colchicine enhanced the toxicity of DTA-RC-ASCNBr-I (33-fold) to a greater extent than that of DTA-ASOR (12-fold). The difference in enhancement by colchicine was also observed in the rate of cell intoxication by the conjugates. Both conjugates were more toxic to the hepatocytes after incubation with the cells at 18 degrees C than at 37 degrees C. In the presence of vanadate (0.2 mM), which enhanced diacytosis, toxicity of DTA-ASOR decreased by 5-fold. After incubation with the hepatocytes, a partial dissociation of DTA-ASOR was found to occur independently of the receptor-mediated endocytosis. Taken together, these results indicate that diacytosis, subunit dissociation and rapid transport of conjugate toward lysosomes affect kinetically the rate of accumulation of the conjugate into a yet unidentified compartment of toxin translocation.

Animals↗
PubMed1994

Characterization of the release of cholecystokinin from a murine neuroendocrine tumor cell line, STC-1.

The murine neuroendocrine cell line, STC-1, was found to contain 296.8 +/- 1.8 fmol of cholecystokinin-like immunoreactivity (CCK-LI) per mg cell protein. Immunocytochemical stain of STC-1 cells maintained in monolayer culture indicated that CCK-LI activity was present in 93% of the cells. Analysis by reverse-phase high-performance liquid chromatography indicated that STC-1 cells contained CCK-8 and an unidentified form as the predominant storage form. form. However, only CCK-8 was released into the culture medium upon stimulation by various secretagogues. The release of CCK-LI from STC-1 cells was stimulated by dibutyryl cAMP, forskolin, KCl, A23187, 4 beta-phorbol 12-myristate 13-acetate and luminal stimulants, e.g., sodium oleate, L-tryptophan, camostat and plaunotol. The release of CCK-LI from STC-1 cells was also stimulated by a neuropeptide, bombesin. The stimulatory effects of most of these agents were dose dependent. The stimulatory effects of dibutyryl cAMP, forskolin, and plaunotol were potentiated by 3-isobutyl-1-methyl xanthine, while that of camostat was not. The results obtained in this study indicate that the release of CCK from STC-1 cells shares the same characteristics of CCK release as from the CCK-secreting cells of the intestinal mucosa observed both in the dog and the rat in vitro and in vivo. Thus, the cellular mechanism of CCK release which appears to be cAMP- and Ca(2+)-dependent may be modulated by cellular protein kinase C activity. The STC-1 cell appears to be a suitable model for studying the mechanism of CCK release.

Animals↗
PubMed1994

Physiological role of cholecystokinin on gastric emptying and acid output in dogs.

We investigated the physiological role of cholecystokinin (CCK) on gastric emptying and acid secretion in seven conscious dogs with gastric cannulae. Two hundred milliliters of a 4% amino acid meal was given via the cannula, and both gastric emptying and acid output were measured concurrently using a dye-dilution technique. Gastric emptying of the liquid amino acid meal was exponential, and the acid output and plasma concentrations of CCK, gastrin, and somatostatin peaked within 30 min after the meal. Intravenous infusion of CCK-8 at 28 and 56 pmol/kg/hr but not 14 pmol/kg/hr increased plasma levels of the peptide and inhibited gastric emptying as well as acid output. Plasma gastrin was not affected significantly by the CCK infusion, whereas plasma somatostatin increased significantly in response to 56 pmol/kg/hr of CCK-8. Loxiglumide, 22 mumol/kg/hr, significantly enhanced gastric emptying and augmented acid output, as well as plasma gastrin response, whereas it abolished the postprandial rise in plasma somatostatin. We concluded that in dogs, CCK plays an important role in the physiologic regulation of postprandial gastric emptying of a liquid caloric meal and acid output. Its inhibitory effect on gastric acid secretion appears to be mediated, at least in part, by somatostatin.

Animals↗
PubMed1994

Roles of gut hormones in negative-feedback regulation of pancreatic exocrine secretion in humans.

BACKGROUND/AIMS: Secretin has been shown to mediate feedback control of pancreatic secretion of fluid and bicarbonate in rats, guinea pigs, and dogs. However, little is known about secretin in the feedback regulation in humans. We investigated the roles of secretin, cholecystokinin, neurotensin, and pancreatic polypeptide on feedback regulation of pancreatic secretion in 10 human volunteers. METHODS: A 5-lumen tube was positioned in the proximal jejunum of fasting subjects under fluoroscopy so that gastric juice via lumen 1 and duodenal contents via lumen 3 were collected separately in 15-minute samples while polyethylene glycol solution was infused into duodenum via lumen 2. An acidified (pH 2.0) 4.25% amino acid mixed with phenol red was infused into proximal jejunum via lumen 4, which was alternated with NaHCO3 (control solution) or trypsin (test solution) via lumen 5 intermittently every 15 minutes during separate test periods. RESULTS: Infusion of control solution significantly increased both bicarbonate (total change [delta], 7799 +/- 1400 mumol/h) and chymotrypsin (delta 5500 +/- 762 mumol/h) outputs and levels of all four plasma hormones. The test solution significantly inhibited both bicarbonate (delta 2999 +/- 700 mumol/h; P < 0.01) and chymotrypsin output (delta 1000 +/- 120 U/h, P < 0.01), which coincided with a significant suppression of plasma concentration of secretin and cholecystokinin but not pancreatic peptide and neurotensin. CONCLUSIONS: A negative-feedback regulation of pancreatic secretion of bicarbonate and enzyme occurs in humans and is mediated via both secretin and cholecystokinin.

Adolescent↗