Exocrine Secretion Of Pancreas Research Articles

Secretion of the Human Exocrine Pancreas in Health and Disease

Secretion of the Human Exocrine Pancreas in Health and Disease

The relationship between cholecystokinin secretion and pancreatic [11C]methionine uptake in patients after partial pancreaticoduodenectomy.

The pancreatic uptake of [11C]methionine ([11C]MET) is associated with beta-cell function and insulin secretion, but [11C]MET uptake and its relationship with exocrine pancreatic performance are less well studied. The postprandial release of cholecystokinin (CCK) depends on gastric emptying velocity and triggers exocrine pancreas secretion. Therefore, we assumed that high postprandial CCK concentrations stimulate the uptake of [11C]MET in the residual pancreas following pancreaticoduodenectomy. Nineteen tumor-free patients after pancreaticoduodenectomy (median age: 64; 25/75 quantile: 56-67years); ten males, nine females and ten healthy controls (median age: 24; 25/75 quantile: 23.8-26years) were given a mixed meal. Plasma CCK, insulin and glucose concentrations were measured before and at 10, 20, 30, 60, 90, 150 and 180min after ingestion. Simultaneously, 800MBq of [11C]MET were administered and the activity [maximum tissue standardized uptake values (SUVmax)] over the pancreas was measured using PET-CT at 15, 30 and 60min after injection. Integrated CCK (AUC30) correlated with SUVmax (AUC60, R2 = 0.45, p value = 0.0013). Multivariate analysis revealed postprandial insulin (AUC60) and CCK concentrations and young age as significant independent predictors of [11C] methionine uptake. The association between CCK concentrations and pancreatic [11C]MET uptake might indicate a causal relationship. Further research should assess whether [11C]MET uptake could serve as a less invasive tool to assess exocrine pancreas activity.

Neurodystrophic component of pathogenesis of the acute postoperative pancreatitis and its prevention by epidural anesthesia

The data on the etiology and pathogenesis of acute postoperative pancreatitis (APP) are analyzed. It is noted that in its pathogenesis, currently, the main attention is paid to the factors of aggression in the pancreas: the activation of proteolytic enzymes and autocatalytic reactions leading to damage of the acinous cells, microcirculation disturbance, and enhancement of free radical oxidation. This determines the prevention and treatment of acute postoperative pancreatitis with the use the inhibition of protease and exocrine secretion of pancreas, antioxidants and cytostatics. Biochemical mechanisms of resistance of the pancreas tissue to damage are given much less attention. The authors substantiate the proposition that organ tissue resistance, besides adequate microcirculation and oxygenation, is determined by the mechanisms of nerve tropism mediated through the sympathetic nervous system. Experimental and clinical data are presented that irritation of the reflexogenic pyloroduodenal zone, in particular during operations in conditions of inadequate anesthesia, leads to hyper activation of the sympathetic nervous system, increased release of the noradrenaline, subsequent depletion of its content in the pancreas tissues. Therefore adrenergic support of trophic (energy and plastic processes) in the pancreas is disrupted, contributing to the development of postoperative complications, including acute postoperative pancreatitis. Taking into account that epidural anesthesia performs afferent and efferent, including sympathetic, blockades; the substantiations are given for use epidural anesthesia for acute postoperative pancreatitis prevention in abdominal operations in combination with the components of general anesthesia.

Radiotherapy is One of the Effective and Common Measures of Pancreatic Cancer Therapy: Iodine-125 (125i) Brachytherapy Improves Local Control and Increase Survival

Introduction: The malignant tumors of torment and life taking pancreatic cancer account for adeno-carcinoma which finds its origin in the exocrine secretions of pancreas. Though a lot many techniques and methodologies are surfacing in the field of medical science but still the overall survival rate is not remarkable. The recommended treatment for local tumor control is the implantation of the I125 radioactive seed (brachytherapy) in the effected organ.Objective: This study was carried out in order to reveal the individual and synergistic efficacy of I125 and ING4 for the treatment of pancreatic cancer tumors. Both in vitro (pancreatic cell lines) and in vivo (in mouse model) investigations were performed.Material and methods: The vibrant combination of ING4 and radiotherapy with I125 for treating pancreatic cancer had been done before this appraisal unknown. We investigated that whether ING4 and I125 radiotherapy treatment can suppress Panc-1 pancreatic cancer cell tumor growth or not using in vitro and in vivo substrates.Results: In this study, we demonstrated that either ING4 or (125)I radiotherapy treatment could induce Panc-1 pancreatic cancer cell growth suppression and apoptosis in vitro. The outcomes revealed that both treatments inhibited can inhibit the malignancy of pancreatic cancer with their tumor suppressive functions. Hence (ING4) gene therapy plus (I125) radiotherapy had produced synergistic effects.

Transposition of a pancreas transplant from the bladder to the terminal ileum twenty years after combined allogenic kidney-pancreas-transplantation

Introduction During the first years of combined allogenic kidney-pancreas-transplantation bladder diversion of the exocrine pancreas secretion was used. After reporting urological and systemic complications it was switched to an enteric diversion with excellent results of pancreas function. Today enteric diversion of the pancreatic ductal secretion is the standard procedure. Nevertheless there are still patients alive with bladder diversion from the early years of transplantation with a good pancreatic function but loss of kidney function. This case describes such a patient and how we dealt with the problem. Case description A 53-year old male patient presented with a progressive renal failure twenty years after combined allogenic kidney-pancreas-transplantation with bladder diversion of the exocrine pancreas secretions. Urine excretion was declining with a pre-dialysis renal failure. Still the pancreas transplant was working properly without the need of insulin therapy. We therefore carried out a separation of the graft duodeno-cystostomy and re-established diversion by a side-to-side graft duodenal-recipient ileal anastomosis. This was done by a 2-layer hand sewn technique. Bladder catheter, drainage near the bladder and drainage near the anastomosis were removed after 5, 8 and 10 days respectively. The pancreas showed proper function without the need of insulin therapy. The patient was released from hospital 14 days after the operation. Results and Conclusions Transposition of a pancreas transplant from the bladder to the terminal ileum twenty years after primary transplantation is technically possible. In this case it was also reasonable in order to protect the bladder from the aggressive pancreatic ductal secretion. Because of the declining urine excretion due to progressive failure of the kidney transplant the exocrine secretion was not properly diluted anymore with the risk of hematuria, lower urinary tract infections, reflux-associated pancreatitis and transitional cell dysplasia. These conditions could limit the opportunity for the patient for a second kidney donation. Take home message Transposition of a pancreas transplant from the bladder to the terminal ileum twenty years after primary transplantation is technically possible and reasonable to offer the patient a chance for a second kidney donation.

A soluble form of human nectin-2 impairs exocrine secretion of pancreas and formation of zymogen granules in transgenic mice

Transgenic mouse lines expressing a soluble form of human nectin-2 (hNectin-2Ig Tg) exhibited distinctive elevation of amylase and lipase levels in the sera. In this study, we aimed to clarify the histopathology and to propose the transgenic mouse lines as new animal model for characteristic pancreatic exocrine defects. The significant increase of amylase and lipase levels in sera of the transgenic lines approximately peaked at 8 weeks old and thereafter, plateaued or gradually decreased. The histopathology in transgenic acinar cells was characterized by intracytoplasmic accumulation of abnormal proteins with decrease of normal zymogen granules. The hNectin-2Ig expression was observed in the cytoplasm of pancreatic acinar cells, which was consistent with zymogen granules. However, signals of hNectin-2Ig were very weak in the transgenic acinar cells with the abnormal cytoplasmic accumulaion. The PCNA-positive cells increased in the transgenic pancreas, which suggested the affected acinar cells were regenerated. Acinar cells of hNectin-2Ig Tg had markedly small number of zymogen granules with remarkable dilation of the endoplasmic reticulum (ER) lumen containing abundant abnormal proteins. In conclusion, hNectin-2Ig Tg is proposed as a new animal model for characteristic pancreatic exocrine defects, which are due to the ER stress induced by expression of mutated cell adhesion molecule that is a soluble form of human nectin-2.

Long-Term Observation on the Development of 24-Hour Ambulatory Blood Pressure Monitoring after Primary SPK with Special Regard to Antihypertensive Treatment and the Type of Exocrine Drainage

Introduction: Cardiovascular disease (CVD) is a leading cause of death in patients with type 1 diabetes. Regarding cardiovascular risk profile as well as patient survival SPK was shown to be superior to kidney transplantation alone or to dialysis therapy in type 1 diabetics. One major cardiovascular risk factor is arterial hypertension. Some but not all small studies with short-term observation and single blood pressure readings (RR) indicated that there might be a reduction of RR after successful SPK, which in addition might be influenced by the type of exocrine drainage of the pancreas secretion. We here present the longterm follow-up results of 24-hour ambulatory blood pressure monitoring (ABPM) in 90 SPK patients. Methods: In this retrospective study we analysed patient and graft survival as well as cardiovascular risk factors of 90 patients with type 1 diabetes who consecutively underwent primary SPK between 1995 and 2000 with a median follow-up of 9.4 years. Before and every year after SPK we analysed systolic, diastolic blood pressure (BP) and mean arterial pressure (MAP) by ABPM, antihypertensive medication and several possibly associated factors of influence on BP control. Results: Survival of patients/PTX/KTX was 87/75 /79 % after 9.4 years (not censored for death). BP regulation was significantly improved over the long-term follow-up after transplantation [87% with a BP level >130/80 mmHg before compared to an average of 30% in the followup period after SPK; median BP was 138/81 mmHg (MAP 100 mmHg) before and 123/72 mmHg (MAP 89 mmHg) during the follow-up period after SPK]. However the dipper/non-dipper ratio did not change. Compared to patients with enteric drainage (ED) of the exocrine pancreas secretion the subgroup of patients with bladder drainage (BD) showed significant lower systolic BP and took smaller numbers of antihypertensive agents. Further factors associated with BP control are shown in table 1.Conclusion: To our knowledge this is the first study, which confirms in a long-term follow-up and by ABPM the beneficial effects of SPK on BP and antihypertensive treatment. Furthermore there are indicators, that bladder drainage has more impact on lowering BP than enteric drainage of the exocrine pancreas secretion. Normalisation of glucose metabolism and its effects are probably the most important factors leading to these results.

Digestive manifestations of parathyroid disorders

The parathyroid glands are the main regulator of plasma calcium and have a direct influence on the digestive tract. Parathyroid disturbances often result in unknown long-standing symptoms. The main manifestation of hypoparathyroidism is steatorrhea due to a deficit in exocrine pancreas secretion. The association with celiac sprue may contribute to malabsorption. Hyperparathyroidism causes smooth-muscle atony, with upper and lower gastrointestinal symptoms such as nausea, heartburn and constipation. Hyperparathyroidism and peptic ulcer were strongly linked before the advent of proton pump inhibitors. Nowadays, this association remains likely only in the particular context of multiple endocrine neoplasia type 1/Zollinger-Ellison syndrome. In contrast to chronic pancreatitis, acute pancreatitis due to primary hyperparathyroidism is one of the most studied topics. The causative effect of high calcium level is confirmed and the distinction from secondary hyperparathyroidism is mandatory. The digestive manifestations of parathyroid malfunction are often overlooked and serum calcium level must be included in the routine workup for abdominal symptoms.

Effect of P2X7receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands

The purinergic P2X(7) receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X(7) receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X(7) receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X(7)(-/-) (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca(2+) activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X(7)(-/-) mice, and in contrast, tear secretion was increased in P2X(7)(-/-) mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X(7) receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X(7) receptor expression. ATP and carbachol increased intracellular Ca(2+) activity, but responses depended on the gland type, presence of the P2X(7) receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X(7) receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X(7) receptor is suppressed in females. We conclude that the P2X(7) receptors are important in short-term physiological regulation of exocrine gland secretion.

Duck Pancreatic Acinar Cell as a Unique Model for Independent Cholinergic Stimulation–Secretion Coupling

This paper investigated the role of acetylcholine (ACh) in physiological regulation of amylase secretion in avian exocrine pancreas. In the isolated duck pancreatic acini, ACh dose dependently stimulated amylase secretion, with a maximal effective concentration at 10 muM. The cAMP-mobilizing compounds forskolin, vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase activating peptide (PACAP) receptor (VPAC) agonists PACAP-38 and PACAP-27 had no effect on the dose-response curve. ACh dose dependently induced increases in cytosolic Ca(2+) concentration ([Ca(2+)]( c )), with increasing concentrations transforming oscillations into plateau increases. Forskolin (10 muM), PACAP-38 (1 nM), PACAP-27 (1 nM), or VIP (10 nM) alone did not stimulate [Ca(2+)]( c ) increase; neither did they modulate ACh-induced oscillations, nor made ACh low concentration effective. These data indicate that ACh-stimulated zymogen secretion in duck pancreatic acinar cells is not subject to modulation from the cAMP signaling pathway; whereas it has been widely reported in the rodents that ACh-stimulated exocrine pancreatic secretion is significantly enhanced by cAMP-mobilizing agents. This makes the duck exocrine pancreas unique in that cholinergic stimulus-secretion coupling is not subject to cAMP regulation.

Effect of tetramethylpyrazine on exocrine pancreatic and bile secretion.

To investigate the effect of tetramethylpyrazine (ligustrazine, TMP) on the secretion of exocrine pancreas (and biliary). In in vivo study, we investigated the effect of TMP on the secretion of pancreatic-bile juice (PBJ) in rats. Using human pancreatic duct cell line, CAPAN-1, combined with the short-circuit current (ISC) technique we further studied the effect of TMP on the pancreatic anion secretion. Administration of TMP (80 mg/kg, i.p.) significantly increased the secretion of PBJ (P<0.05), but the pH of PBJ and the secretion of pancreatic protein were not significantly affected. Basolateral addition of TMP produced a dose-dependent increase in ISC (EC50=1.56 mmol/L), which contained a fast transient ISC response followed by a slow decay. Apical application of Cl- channel blockers, DPC (1 mmol/L), decreased the response by about 67.1% (P<0.001), whereas amiloride (100 micromol/L), a epithelial sodium channel blockers, had no effect. Removal of extracellular HCO3- abolished TMP-induced increase in ISC by about 74.4% (P<0.001), but the removal of external Cl- did not. Pretreatment with phosphodiesterase inhibitor, IBMX(0.5 mmol/L), decreased the TMP-induced ISC by 91% (P<0.001). TMP could stimulate the secretion of PBJ, especially pancreatic ductal HCO3- secretion via cAMP or cGMP-dependent pathway. It need further study to investigate the roles of cAMP or cGMP in the effect of TMP on the secretion of exocrine pancreas.

Immunohistochemical localization of neuropeptides in bovine pancreas.

The occurrence and density of distribution of nerves and endocrine cells that are immunoreactive for neuropeptides in the bovine pancreas were studied by immunohistochemistry. The six neuropeptides localized were galanin (GAL), substance P (SP), methionine-enkephalin (MENK), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP). The exocrine pancreas was shown to have an appreciable number of GAL- and SP-immunoreactive nerve fibres but few fibres showing immunoreactivity for VIP and CGRP. Numerous MENK-, GAL-, SP-, and NPY-immunoreactive nerve fibres were seen in the endocrine portion of the pancreas. Nerve cell bodies in the intrapancreatic ganglia showed immunoreactivity for all of the neuropeptides except CGRP. Endocrine cells showing immunoreactivity for GAL and SP were observed in the large islets and islets of Langerhans, respectively. The present results indicate a characteristic distribution of neuropeptides in the bovine pancreas, which may regulate both exocrine and endocrine secretions of pancreas.

On the effect of xenin and xenin fragments on exocrine pancreas secretion in vivo

A stimulatory effect on exocrine pancreas secretion could be demonstrated with high concentrations of the 25-amino-acid peptide xenin in non-anesthetized dogs. This peptide has been isolated from gastric mucosa and it is part of a structural coat protein. It has close structural similarities to neurotensin. The longer C-terminal fragments xenin-(13–25) and xenin-(18–25) are essential for the stimulation of exocrine pancreas secretion in vivo. The smaller peptide fragments xenin-(21–25) and xenin-(22–25) failed to stimulate the pancreas as well as the N-terminal peptide fragment xenin-(1–23). The stimulatory effects of xenin may be mediated via neural neurotensin pathways, because neurotensin receptor blockade abolished the stimulatory effect on pancreatic secretion. Cholinergic pathways are not involved, because atropine had no inhibiting effect.

Sow milk feeding vs. pancreatic exocrine secretion in pigs

Abstract Though milk promotes gastrointestinal tract growth during ontogenic development of mammals, our studies have shown that feeding milk does not stimulate exocrine pancreas secretion in pigs before weaning. To study the mechanisms behind these findings pancreatic secretion was studied in pigs surgically fitted with a pancreatic duct catheter and a duodenal re-entrant cannula. Pancreatic secretion was measured at 1h intervals from the day before to 5 days after weaning. A gradual increase was observed in fluid secretion (ml/kg/h, P

Secretin potentiates guinea pig pancreatic response to cholecystokinin by a cholinergic mechanism

The effects of secretin and cholecystokinin on exocrine pancreas secretion in the guinea pig were investigated. The putative potentiating effect of these two hormones was studied in various settings to elucidate the effect of cholinergic stimuli in such interaction. In anesthetized guinea pig, intravenous infusion of cholecystokinin (0.75 pmol.kg-1.min-1) or secretin (0.5 pmol.kg-1.min-1) resulted in a marked and rapid increase of pancreatic juice flow and protein output. When cholecystokinin was combined with secretin, there was a significant increase in pancreatic, compared with cholecystokinin alone. This increase in pancreatic juice secretion and protein output was significantly suppressed by the prior administration of 100 micrograms/kg atropine. Similar results were obtained when trypsinogen release from pancreatic segments was measured in response to cholecystokinin (32 nM-32 pM) and (or) secretin (1 microM-32 nM). When we assayed the hormonal interaction on amylase release from dispersed pancreatic acini, we found that secretin (32 nM) failed to influence the secretory response to cholecystokinin (1 pM-10 nM). Thus we conclude that a combination of cholecystokinin and secretin resulted in a marked potentiation of the secretory responses in the exocrine guinea pig pancreas by a mechanism that involves cholinergic interactions present at the tissue level but not at the dispersed secretory cell level.

Metallothionein is a component of exocrine pancreas secretion: implications for zinc homeostasis.

Using transgenic mice that overexpress metallothionein-I (MT-I) and zinc-induced normal and transgenic animals, we have explored the localization of MT in the pancreas. Light-level immunocytochemistry demonstrated MT in acinar cells but not islet cells. Immunolabeling also revealed the presence of MT in pancreatic ducts, suggesting that it is released from acinar cells. Ultrastructural immunolocalization showed that MT was cytoplasmic, and no MT immunoreactivity was detected in lumens of the vesicular secretory pathway. Secreted pancreatic juice was collected from pilocarpine-stimulated mice and assayed for MT by a 109Cd-labeled hemoglobin-exchange assay and by radioimmunoassay. Both methods revealed high (> 1,000 ng/ml) levels of MT in the stimulated secretion. The level of MT in pancreatic juice from transgenic mice was only slightly (2-fold) increased despite dramatic overexpression of MT-I in the pancreas (> 20-fold). In contrast, zinc induction of MT significantly increased MT by 5- to 10-fold in the pancreatic juice, in normal and transgenic mice. These data indicate that MT is released from pancreatic acinar cells but not by the classical vesicular secretory pathway. In addition, MT levels in pancreatic juice are regulated by zinc, suggesting a physiological role of the pancreas in metal homeostasis.

Development and regulation of porcine pancreatic function.

A surgical and experimental procedure was developed to enable the collection of pure and inactivated pancreatic juice during the growth of the pig. Studies have shown that, during the suckling period, both the basal and the secretory responses to suckling are low, if present at all. After weaning, basal levels of the total exocrine secretion, total protein, amylase, and trypsin, respectively, increase slightly, while the postprandial levels of total protein, amylase, trypsin, lipase, colipase, and carboxylester lipase, respectively, increase markedly. The pancreatic juice enzyme composition changes qualitatively and the antibacterial activity of the pancreatic juice also significantly increases. Piglet age appeared to be of minor importance, since weaning at either 4 or 6 wk of age gave the same results. Secretin and CCK administered together in supraphysiological doses only significantly affect exocrine function from 3-4 wk of age. However, CCK may also affect the exocrine pancreas indirectly via reflexes initiated intraduodenally. Milk consumption in the suckling pig leads to a postprandial increase in glucose levels but not insulin. Milk appears to be able to regulate the exocrine pancreas to produce only the amount and type of enzymes required for digestion. Thus, milk components or digestive products may affect pancreas function regulation. Studies show that enterostatin, the procolipase activation peptide, may inhibit pancreatic secretion mediated indirectly through the GI tract. Pancreastatin, an endocrine peptide, inhibits both insulin secretion and protein and trypsin secretion to pancreatic juice. In hypoinsulinemic (alloxan+streptozotocin diabetes) pigs (15-20 kg), no postprandial pancreatic juice response is seen, although CCK 33 + secretin can stimulate pancreatic secretion. Hypoinsulinemic pigs have a reduced capacity for glucose tissue utilization, suggesting that tissue metabolism and exocrine pancreas secretion are related.

On the effect of xenin on exocrine pancreas secretion

On the effect of xenin on exocrine pancreas secretion

Inhibition by somatostatin of amylase secretion induced by calcium and cyclic AMP in rat pancreatic acini.

It has recently been shown that somatostatin inhibits amylase secretion from isolated pancreatic acini by reducing cyclic AMP (cAMP) production [Matsushita, Okabayashi, Hasegawa, Koide, Kido, Okutani, Sugimoto and Kasuga (1993) Gastroenterology 104, 1146-1152]. To date, however, little is known as to the other mechanism(s) by which somatostatin inhibits amylase secretion in exocrine pancreas. To investigate the action of somatostatin independent of cAMP generation, we examined the effect of somatostatin in isolated rat pancreatic acini stimulated by 1 microM calcium ionophore A23187 and 1 mM 8-bromo-cyclic AMP (8Br-cAMP). Somatostatin inhibited amylase secretion evoked by a combination of A23187 and 8Br-cAMP in a dose-dependent manner. The maximum inhibition was obtained by 10(-7) M somatostatin, and at this concentration somatostatin inhibited the effect of A23187 and 8Br-cAMP by approximately 30%. In electrically permeabilized acini, an elevation of free calcium concentration resulted in an increase in amylase secretion and cAMP enhanced the secretion evoked by calcium. cAMP shifted the dose-response curve for calcium-induced secretion leftwards and elevated the peak value of secretion. Somatostatin inhibited the effect of cAMP on calcium-induced amylase secretion by shifting the dose-response curve to the right. To determine the involvement of a G-protein(s), we examined the effect of somatostatin in acini pretreated with pertussis toxin. Pretreatment of acini with pertussis toxin completely blocked somatostatin-inhibition of amylase-secretion evoked by A23187 and 8Br-cAMP. These results indicate that somatostatin decreases amylase secretion induced by cAMP and calcium by reducing the calcium sensitivity of exocytosis. A pertussis toxin-sensitive G-protein is also involved in this step.

Evidence for an apical, nonregulated protein secretion in pig exocrine pancreas.

Secretory proteins are segregated into two pathways out of the trans-Golgi network of regulated secretory cells. To identify proteins specifically secreted by pathways other than the one leading to zymogen granule exocytosis in the exocrine pancreas, conscious permanently cannulated pigs were perfused with atropine to inhibit the regulated fusion of granules. Atropine almost totally inhibited the protein secretion after 1 h of perfusion. The secretion of GP-2, a glycosyl phosphatidylinositol-anchored protein of the zymogen granule membrane, was partially inhibited but was never totally abolished by atropine perfusion. The pattern of proteins secreted under atropine was almost totally different. Soluble GP-2 was the major secretory product. Its specific activity increased 60 times over its normal level in all other conditions. This secretion clearly originated from nonregulated pathways. Results suggest that during the atropine block the apical plasmalemma could be the source of the released GP-2 and that the sustained nature of this release is compatible with a replenishment of the plasmalemma with GP-2 by the continuous exocytosis of vesicles from the nonregulated pathways.