Regulation Of Pancreatic Secretion Research Articles

Material basis and molecular mechanism of Dachengqi Decoction in treatment of acute pancreatitis based on network pharmacology

The network pharmacology was used to investigate the material basis and molecular mechanism of Dachengqi Decoction(DCQD) in the treatment of acute pancreatitis(AP). Potential targets of components from DCQD and relevant pathogenic genes of AP were identified through database retrieval. Then, crucial targets were verified with relevant active chemical components via molecular docking. DAVID database was used to explore the functions and pathways involved in the treatment of AP. A total of 108 components were correlated with 28 targets. Molecular docking showed a strong binding ability of key targets and their corresponding compounds. DAVID enrichment analysis showed 438 biological process, 31 molecular functions, 17 cellular components and 96 KEGG pathways. DCQD may achieve its pharmacological effects through anti-inflammatory and anti-oxidative effects, negative regulation of apoptosis and regulation of pancreatic secretion, involving multiple signals, such as IL-17, TNF and NF-κB signaling pathway. In this study, it is the first time to use the method of network pharmacology to reveal the molecular mechanism of DCQD in the treatment of AP by multiple components and multi-signaling pathways, which provides a basis for further biological experiments of AP.

The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells.

Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl− channels important for anion secretion, we herein performed experiments on Capan-1, a human pancreatic duct cell line, using open-circuit Ussing chamber and gramicidin-perforated patch-clamp techniques. The luminal addition of adenosine increased the negative transepithelial potential difference (Vte) in Capan-1 monolayers with a half-maximal effective concentration value of approximately 10 μM, which corresponded to the value obtained on whole-cell Cl− currents in Capan-1 single cells. The effects of adenosine on Vte, an equivalent short-circuit current (Isc), and whole-cell Cl− currents were inhibited by CFTRinh-172, a cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel inhibitor. The adenosine A2B receptor agonist, BAY 60-6583, increased Isc and whole-cell Cl− currents through CFTR Cl− channels, whereas the A2A receptor agonist, CGS 21680, had negligible effects. The A2B receptor antagonist, PSB 603, inhibited the response of Isc to adenosine. Immunohistochemical analysis showed that the A2A and A2B receptors colocalized with Ezrin in the luminal membranes of Capan-1 monolayers and in rat pancreatic ducts. Adenosine elicited the whole-cell Cl− currents in guinea pig duct cells. These results demonstrate that luminal adenosine regulates anion secretion by activating CFTR Cl− channels via adenosine A2B receptors on the luminal membranes of Capan-1 cells. The present study endorses that purinergic signaling is important in the regulation of pancreatic secretion.

Recent advances in the regulation of pancreatic secretion.

This review highlights recent progress made in the field of pancreatic secretion. This review summarizes a number of recent studies demonstrating the intracellular pathways by which hormones and neural inputs regulate pancreatic exocrine and endocrine secretion. In particular, the effects of vasoactive intestinal peptide and secretin on intra-acinar cell adenosine 3',5'-cyclic monophosphate are explored. Considerable attention is paid to regulation of β-cell function and includes studies detailing the mechanisms of regulation of insulin by somatostatin, serotonin, and melanocortins. These studies emphasize the critical role that hormonal, paracrine, and neural factors play in glucose homeostasis. Exocrine and endocrine pancreatic secretions are regulated by hormonal and neural mechanisms, and understanding these pathways will enable the discovery and design of new and improved therapies for prevention and control of diabetes and perhaps exocrine insufficiency.

Modulation of pancreatic exocrine and endocrine secretion

Recent advances in the regulation of pancreatic secretion by secretagogues, modulatory proteins and neural pathways are discussed. Downstream events involved in secretagogue stimulation of pancreatic secretion have been elucidated through characterization of the Src kinase pathway. An additional mechanism regulating vagus nerve effects on the pancreas involves Group II and III metabotropic glutamate receptors that are located presynaptically on certain vagal pancreas-projecting neurons. Hypothalamic neurons perceive glucose and regulate insulin release by direct communication with islets, and activation of proopiomelanocortin neurons by leptin enhances insulin secretion and modulates glucose but not energy homeostasis. Ghrelin and somatostatin mediate glucose-stimulated insulin secretion by differential receptor signaling that is dependent on the amount of ghrelin and state of receptor heterodimerization. Endoplasmic reticulum (ER) stress and loss-of-function mutations of a key ER stress protein are associated with disruption of membrane translocation and reduction in insulin secretion. The importance of hormones, neuropeptides, amino acids, cytokines and regulatory proteins in pancreatic secretion and the pathophysiology of type 2 diabetes are also discussed. The biomolecular pathways regulating pancreatic secretions are still not fully understood. New secretagogues and mechanisms continue to be identified and this information will aid in drug discovery and development of new and improved therapy for pancreatic disorders.

Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe Deer

BackgroundPhysiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf) belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication.ResultsForty bovine were distributed into 2 groups of animals either fed exclusively with a milk formula (monogastric) or fed a dry feed which allowed for rumen function to develop, they were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in the temperate broadleaf and mixed forests, shot during the hunting season and classified in two groups adult and young. Immediately after death, the pancreas was removed for tissue sample collection and then analyzed. When expressed in relation to body weight, pancreas, pancreatic protein weights and enzyme activities measured were higher in Roe deer than in calf. The 1st original feature is that in Roe deer, the very high content in pancreatic enzymes seems to be related to specific digestive products observed (proline-rich proteins largely secreted in saliva) which bind tannins, reducing their deleterious effects on protein digestion. The high chymotrypsin and elastase II quantities could allow recycling of proline-rich proteins. In contrast, domestication and rearing cattle resulted in simplified diet with well digestible components. The 2nd feature is that in wild animal, both receptor subtypes of the CCK/gastrin family peptides were present in the pancreas as in calf, although CCK-2 receptor subtype was previously identified in higher mammals.ConclusionsBovine species could have lost some digestive capabilities (no ingestion of great amounts of tannin-rich plants, capabilities to secrete high amounts of proline-rich proteins) compared with Roe deer species. CCK and gastrin could play an important role in the regulation of pancreatic secretion in Roe deer as in calf. This work, to the best of our knowledge is the first study which compared the Roe deer adaptation to diet with a domesticated animal largely studied.

The Most Important Duty of a Mentor Remains His Availability: An Interview with Dr. Jean Morisset

We interview Dr. Jean Morisset, an internationally recognized leader in the field of pancreatic physiology. His work on the regulation of pancreatic secretion by hormones and the parasympathetic nervous system has been fundamental to the understanding of pancreatic adaptation to diet in normal as well as pathological conditions. Here he provides advices for young investigators starting in the field of pancreatic research and emphasizes the key role of the relationship mentor-mentee during the career development.

EFFECT OF RENIN-ANGIOTENSIN SYSTEM ON REGULATION OF PANCREATIC SECRETION IN CONSCIOUS RATS

Background/Aim: Although previous studies have shown the presence of renin-angiotensin system (RAS) in the pancreas, the effect of RAS on regulation of pancreatic secretion has remained controversial. In the present study, we therefore investigated the effect of RAS on pancreatic secretion by using valsartan, a specific angiotensin II receptor blocker in conscious rats. Method: Male Wistar rats prepared with pancreatic, bilialy, duodenal, and intravenous cannulas were used in the study. Valsartan at a dose of 0, 1, 5, or 25 mg/kg was administrated into the duodenum, and volume of pancreatic fluid and protein output were determined for 4 hours. In addition, to examine the mechanism of action of RAS on pancreatic secretion, perivagal application of capsaicin (1 mg/rat) or intravenous infusion of atropine (100 μg/kg/hr) was conducted and then pancreatic secretion was examined after administration of valsartan at 25 mg/kg. Furthermore, to examine the influence of RAS on CCK or secretin-stimulated pancreatic secretion, valsartan at 25mg/kg was administrated and then pancreatic secretion was examined during intravenous infusion of CCK or secretin. Results: Pancreatic fluid secretion, but not protein output significantly decreased after administration of valsartan at 5 and 25 mg/kg. Perivagal application of capsaicin and intravenous infusion of atropine completely abolished the decrease in the pancreatic fluid secretion by valsartan. Valsartan at 25 mg/kg did not exert any effects on the CCK or secretin-stimulated pancreatic secretion. Conclusion: Present results suggest that pancreatic RAS participates in the stimulation of basal pancreatic fluid secretion via cholinergic pathway and has no influence on CCK or secretin-stimulated pancreatic secretion in conscious rats.

Ileal exposure to pig pancreatic juice and bile inhibit exocrine pancreatic secretion in pigs

The mechanisms involved in the down regulation of the exocrine pancreas are still not fully elucidated. The purpose of the present study was to examine the effect of duodenal and ileal exposure to pancreatic enzymes and bile on pancreatic secretion. Experiments were performed with pigs fitted with pancreatic duct, ileal and jugular vein catheters, and duodenal T-shaped cannula. A negative feedback regulation of pancreatic secretion was found for both duodenal and ileal delivery of pancreatic juice. Pancreatic secretion was unaffected by duodenal delivery of bile and bile salts, while ileal delivery of bile and bile salts lowered it. On the other hand, pancreatic secretion was increased by duodenal loading of commercial non- or activated pancreatic enzyme preparations, thus probably recognised as dietary protein. Plasma cholecystokinin (CCK) level was lowered only by duodenal delivery of pancreatic juice. In conclusion, the results prove the existence of negative feedback mechanism regulating pancreatic secretion dependent on the presence of pure pancreatic juice or bile at the ileal level. The mechanism at the duodenal level is exclusively sensitive to pure pancreatic juice. (c) 2007 Elsevier B.V All rights reserved. (Less)

Fluorescent Indicators Distributed throughout the Pharmacophore of Cholecystokinin Provide Insights into Distinct Modes of Binding and Activation of Type A and B Cholecystokinin Receptors

Ligand probes with fluorescent indicators positioned throughout the pharmacophoric domain can provide important insights into the molecular basis of receptor binding and activation as reflected in the microenvironment of each indicator while docked at a receptor. We developed three cholecystokinin-like probes with Aladan situated at the N terminus, in the mid-region, and at the C terminus (positions 24, 29, and 33, respectively). These were studied in solution and docked at type A and B cholecystokinin receptors. This study demonstrated clear differences in mechanisms of cholecystokinin binding and activation of these structurally related receptors with distinct agonist structure-activity relationships. The fluorescence characteristics of Aladan are highly sensitive to the polarity of its microenvironment. The mid-region probe was least accessible to the aqueous milieu as determined by fluorescence emission spectra and iodide quenching, which was not altered by changes in conformation from active to inactive. Accessibility of the N- and C-terminal probes was affected by receptor conformation. The position 24 probe was more easily quenched in the active than in the G protein-uncoupled conformation for both receptors. However, the position 33 probe docked at the type A cholecystokinin receptor was more easily quenched in the active conformation, whereas the same probe docked at the type B cholecystokinin receptor was more easily quenched in the inactive conformation. Fluorescence anisotropy and red edge excitation shift determinations confirmed these observations and supported the proposed movements. Although both type A and B cholecystokinin receptors bind cholecystokinin with high affinity, resulting in fully efficacious biological responses, these receptors utilize distinct molecular modes of binding.

Regulation of pancreatic secretion in vitro by nociceptin/orphanin FQ and opioid receptors: A comparative study

The effects of nociceptin/orphanin FQ (N/OFQ) on gastrointestinal functions resemble those of classic analgesic opioid agonists. In this study, we compared changes in amylase release from guinea pig isolated pancreatic acini and lobules induced by the N/OFQ analogue [Arg 14,Lys 15]N/OFQ and by the delta-receptor opioid agonist deltorphin. Carbachol strongly stimulated amylase release from isolated acini. Both peptides left baseline and carbachol-stimulated amylase secretion from pancreatic acini unchanged. Co-incubation of KCl-stimulated lobules with [Arg 14,Lys 15]N/OFQ or deltorphin inhibited KCl-induced amylase release in a concentration-dependent manner. Although maximal inhibition of amylase release by [Arg 14,Lys 15]N/OFQ and deltorphin had similar amplitude, [Arg 14,Lys 15]N/OFQ was 100-fold more potent than deltorphin on a molar basis. The selective NOP-receptor antagonist [Nphe 1,Arg 14,Lys 15]N/OFQ-NH 2 (UFP-101) antagonized [Arg 14,Lys 15]N/OFQ-induced inhibition but left deltorphin-induced inhibition unchanged. The selective delta opiate receptor antagonist naltrindole had no effect on [Arg 14,Lys 15]N/OFQ inhibition but partly prevented the inhibition by deltorphin. [Arg 14,Lys 15]N/OFQ and deltorphin combined had no influence on each other. These findings show that [Arg 14,Lys 15]N/OFQ inhibits pancreatic enzyme secretion by suppressing cholinergic transmission in intralobular nerve fibers, as previously reported for opioid agents. They suggest that [Arg 14,Lys 15]N/OFQ inhibition of amylase release is mediated through the NOP receptor and not through the delta opioid receptor. The N/OFQ-NOP receptor system, like the delta opioid system, plays an inhibitory role in regulating exocrine pancreatic secretion.

CHRONIC HELICOBACTER PYLORI INFECTION DOES NOT INCREASE THE RISK TO DEVELOP PANCREATIC CANCER.

Background:Helicobacter (HP) infection is associated with a 4–6 time increased risk of gastric cancer most probably via the effects of chronic inflammation. HP infection leads to atrophic changes in the gastric mucosa and in the long run decreased acid production. Acid is involved in the regulation of pancreatic secretion and HP infection could lead to a disturbed pancreatic secretion. Whether HP infection could be involved in the development of pancreatic cancer has not been fully elucidated. The aim of this study was to investigate the occurrence of HP infection in patients with pancreatic cancer. Methods: A cohort of 33,000 persons in Malmö were examined in a health screening investigation between 1974 and 1992. Blood samples were drawn and serum was stored at −20°C for up to 21 years before analysis. In 2000, 126 cases of pancreatic cancer had been diagnosed in this cohort. Diagnoses were validated through diagnostic records and histology. Serum samples from 87 of the 126 persons that developed pancreatic cancer were identified and 263 serum samples from age, gender and time of sampling matched controls in the same cohort were also obtained. Antibody titers against HP were measured with a regular ELISA Results: The median time between health examination and clinical diagnosis of pancreatic cancer was 12,5 years (0,8–24). The median age of the cases was 60,5 years (45–76). Positive HP serology was seen in 34 of the 87 cases (39,1%) and in 129 of the 263 controls (36,9%). Borderline titers were seen in 9,2% of the cases and 8,9% of the controls. Conclusions: In this relatively young population of pancreatic cancer cases there was no increased incidence of chronic HP infection. Whether HP infection could be a risk factor in an older subgroup of patients with pancreatic cancer will have to await later studies. Totally around 300 incident cases are expected in this cohort with time.

Stimulation of pancreatic secretion by non-sulfated CCK-58 gives insight into neurohormonal regulation of the pancreas

Non-sulfated cbolecystcMmn-58 (CCK-58ns) has been shown to be present m porcine and canine intestine, This form ot cholecystokinin may have been ignored by our laboratory in previous studies because it reacts very poorly in our radioimmunoassay with antibody 5135 (about 10% as potent as CCK-8s. However, it is present in the intestine at about half the concentration of CCK-58s. A maior bi-product from the synthesis and purification of rat CCK-58s is CCK-58ns. Syrabenc CCK-58ns was wall separated from CCK-58s, and was used to stinmlate pancreatic secretion in awake rats. CCK-58ns was as potent and one-half as effacions as CCK.-58s for stimulation ot pancreatic find and protein. CCK-8s was as potent as the CCK-58 peptides for stimulation of prutem, but CCK-8 did not stimulate fluid secretion (Figure). A model that would account tbr these results is one where both the acmar CCK-A receptor and the CCK-A receptor on intrapancreatic nerves regulate pancreatic secretion. The nanral CCK-A receptor is mediated by a neumtransmttter that can be blocked by atropine and it stinmlates both protein and fuid. We propose that this neural receptor is not activated by CCK-8s at any concetrations, possibly because CCK-8s is inactivated by neural endopeptidease before it reaches the neural CCK-A receptor. This is supported by the tact that CCK-58s is resistant to this endopepfidase degradation while CCK-8s is rapidly cleaved. We barther propose that the CCK-A receptor m~ aciuar cells is not activated by CCK-58ns and its inability to react with this receptor causes the decreased efficacy compared to CCK-58s. In conclusion, CCK-58ns is present in intestine and it has a unique pattern for stimulating pancreanc secretion that leads to new hypotheses about regulation of pancreatic secretion.

Proteinase-activated receptor-2 stimulates CCK secretion via Gq/11 and PLC/cPLA2 pathways: Evidence for positive feedback regulation of pancreatic secretion

Proteinase-activated receptor-2 stimulates CCK secretion via Gq/11 and PLC/cPLA2 pathways: Evidence for positive feedback regulation of pancreatic secretion

Neurohormonal control of exocrine pancreas

The exocrine pancreas is regulated by various hormonal factors derived from the gut through hormone-hormonal and neurohormonal interactions. Physiologic stimuli entering the upper small intestine elicit the release of intestinal hormones and activate sensory reflex mechanisms from the intestinal mucosa to stimulate or inhibit exocrine pancreatic secretion. In addition, the endocrine pancreas, intrapancreatic nerves, and some extrapancreatic neural pathways, with or without mediation by the vagus nerve, are known to participate in regulation of exocrine pancreatic secretion. It has been established that two key intestinal hormones, secretin and cholecystokinin (CCK), in physiologic doses, act through the vagal afferent pathway and interact with each other as well as with other gut hormones. The releases of these two hormones are mediated through the corresponding releasing peptides. In the past few years, the roles of secretin- and CCK-releasing peptides have become more clearly defined. The participation of several neurotransmitters and regulatory peptides in the regulation of exocrine pancreatic secretion has also been established. In addition, neurotransmitters and neuropeptides released from the central nervous system may participate in the regulation of pancreatic secretion. It is conceivable that a few neurotransmitters and neuropeptides are involved in each neural regulatory pathway. However, their roles and sites of action in each pathway remain to be determined.

Hypothalamic regulation of pancreatic secretion is mediated by central cholinergic pathway

Hypothalamic regulation of pancreatic secretion is mediated by central cholinergic pathway

Regulation of pancreatic secretion by vagal nerve during short-term duct occlusion in conscious rats.

The basal exocrine secretion of the pancreas is maintained at a constant level in conscious rats. We examined the changes in basal secretion with respect to the effect of various time periods of pancreatic duct occlusion (PDL). Male Wistar rats were prepared with cannulae that separately drained bile and pancreatic juice as well as with a duodenal cannula. Rats were placed in restraint cages, and experiments were conducted without anesthesia 4 days after the operation. Cholecystokinin (CCK) release was artificially prevented by the continuous infusion of bile with trypsin into the duodenal lumen throughout the experimental period to avoid the modification of pancreatic response by CCK. After 2-h basal collection, a pancreatic secretion was interrupted for 0.5-4 h, and then the collection of pancreatic juice was initiated again for an additional 2-4.5 h. The pancreatic secretion after the reopening of the 0.5-to 3-h PDL was comparable to basal secretion levels. However, protein secretion was significantly inhibited after the removal of 4-h PDL. Both vagotomy and capsaicin treatment abolished this inhibition, and the protein secretion after 1-h PDL in vagotomized rats increased 1.5-fold high compared with the basal value. These observations indicate that protein secretion was ceased during PDL via vagal nerve, and this may be a self-protective mechanism.

Neurohumoral control of the exocrine pancreas

Recent advances in the study of pancreatic exocrine secretion are reviewed, with an emphasis on neurohumoral mechanisms. In the past year, cDNA for the human pancreatic sodium-bicarbonate cotransporter was cloned, and the expressed protein was localized to pancreatic acini and ductal cells. Recent information suggests that the cholecystokinin B receptor has a role in pancreatic amylase release. Further evidence supports the concept of a protease-sensitive negative feedback mechanism regulating pancreatic exocrine secretion. Study of the expression of the receptors responsible for the regulation of pancreatic function has proven fruitful in the determination of the molecular mechanisms of hormone signal transduction and desensitization. Studies of peptide 1, pituitary adenylate cyclase-activating peptide, and gastrin-releasing peptide have shown how these peptides participate in the regulation of pancreatic secretion and have provided information on intracellular signaling pathways obtained using rat pancreatic tumor cells. Neural regulation via cholinergic receptors in isolated pancreatic acini and the mechanisms responsible for other neurotransmitters, such as calcitonin gene-related peptide, histamine, and dopamine, are reviewed. This review highlights recent discoveries in the neurohumoral regulation of pancreatic exocrine secretion.

Canine pancreatic juice stimulates the release of secretin and pancreatic secretion in the dog.

A secretin-releasing factor (SRF) was found in canine pancreatic juice that increases plasma secretin and stimulates pancreatic secretion in rats, suggesting that a positive feedback mechanism may be involved in the regulation of pancreatic secretion. In the present study, we investigated to determine whether or not SRF releases endogenous secretin and stimulates exocrine pancreatic secretion in conscious dogs. Fresh pancreatic juice was collected from four dogs by intravenous administration of secretin at 0.5 microg. kg(-1). h(-1) and CCK at 0.2 microg. kg(-1). h. The juice was boiled for 10 min at 100 degrees C. Experiments were carried out in phase I of spontaneous cycle of interdigestive pancreatic secretion. The testing solutions were infused intraduodenally in separate experiments: NaHCO3 solution (0.1 M, 4.5 ml/min, 60 min), a corn oil (Lipomul, 2 ml/min, 10 min), boiled pancreatic juice (BPJ, 4.5 ml/min, 60 min), and mixture of BPJ and Lipomul. Pancreatic secretion of fluid and bicarbonate was significantly increased by either BPJ or a mixture of BPJ and Lipomul (34- and 31-fold or 41- and 38-fold, respectively). Plasma secretin level also significantly increased by 164.7 +/- 13.4% and 223.1 +/- 35.0%, respectively, from basal concentration of 1.7 +/- 0.5 pM. In contrast, neither bicarbonate solution nor Lipomul influenced the plasma secretin level or pancreatic secretion. In addition, when Lipomul was incubated with BPJ, no fatty acid was produced. Thus the increased pancreatic secretion in the dog infused with a combination of BPJ and Lipomul was caused by SRF in BPJ, which released endogenous secretin. Moreover, the increases by BPJ of both plasma secretin level and bicarbonate secretion were completely blocked by intravenous administration of an antisecretin antibody in these dogs. The observations suggest that SRF in pancreatic juice exerts a positive feedback effect on exocrine pancreatic secretion that is mediated by the release of secretin in the interdigestive state in dogs.

Different actions of CCK on pancreatic and gastric growth in the rat: effect of CCK(A) receptor blockade.

1. It is now well established that cholecystokinin (CCK) has a major physiological role in the regulation of pancreatic secretion and gastro-intestinal (GI) motility. Both these actions are mediated by stimulation of CCK(A)-receptors located on pancreatic acini and GI smooth muscle cells. While chronic administration of CCK-like peptides invariably causes pancreatic hypertrophy and hyperplasia, their action on gastric growth remains controversial. 2. In the present investigation the action of exogenous and endogenous CCK on both pancreatic and gastric growth was studied in the same animal. In addition, the ability of dexloxiglumide, a new potent and selective CCK(A)-receptor antagonist, to counteract CCK-mediated effects was evaluated. 3. The amphibian peptide caerulein (1 microg kg(-1) intraperitoneally three times daily) was used as a CCK agonist, while camostate (200 mg kg(-1) intragastrically once daily), a synthetic protease inhibitor, was used to release endogenous CCK. They were administered to rats for seven days with or without dexloxiglumide (25 mg kg(-1) subcutaneously 15 min before the stimulus). On the eighth day, animals were killed, the pancreas and stomach excised, weighed, homogenized and their protein and DNA content measured. 4. Both exogenous and endogenous CCK increased the weight of the pancreas as well as the total pancreatic protein and DNA content. Dexloxiglumide, which alone did not affect pancreatic size and composition, was able to counteract both caerulein- and camostate-induced pancreatic changes. Neither stimuli affected gastric growth in respect of weight and composition of the oxyntic gland area and the antrum. 5. These results show different effects of CCK on pancreatic and gastric growth. The CCK-induced pancreatic hypertrophy and hyperplasia are blocked by the potent and specific CCK(A)-receptor antagonist, dexloxiglumide. This compound therefore represents a useful tool to investigate CCK-receptor interactions in peripheral organs.

Immunocytochemical localization of the NPY/PYY Y1 receptor in the developing pancreas.

Neuropeptide Y, peptide YY, and pancreatic polypeptide are structurally related peptides that are considered to play a role in the regulation of pancreatic secretion and blood flow. Several receptor subtypes for these peptides have been identified, and the Y1, Y2, Y4/PP1, Y5, and Y5/PP2/Y2b receptors are cloned. We have prepared polyclonal peptide antibodies that recognize the Y1 receptor and now report on its localization in the adult and developing rat pancreas. In the adult pancreas, Y1 receptors were detected both in some centroacinar and intralobular duct cells and in endothelial cells. In the developing pancreas (E12.5-E16.5), Y1 receptor immunoreactivity was observed in numerous nonendocrine epithelial cells. These cells occurred in the immediate vicinity of peptide YY-positive endocrine cells. At E16.5, a fraction of these Y1 receptor-containing cells co-stored amylase. One day later, Y1 receptor immunoreactivity became restricted to pancreatic duct-like cells that occurred in close proximity to peptide YY cells. In fetal rats, intense Y1 receptor staining was also observed in endothelial cells. These observations, together with the finding of early pancreatic peptide YY expression, suggest that peptide YY produced by fetal endocrine cells may exert an action on exocrine cells, duct cells and endothelial cells during development.