摘要:

Morphology and structural organization of calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers and islet cells in rat pancreas were analyzed with light and electron microscopic immunocytochemistry. Immunoreactive axons innervate exocrine and endocrine parenchyma, but are most abundant in connective tissue septac between pancreatic lobules and within the perivascular space of small arterioles. In the stromal compartment and perivascular space, immunoreactive product is confined to thin, unmyelinated axons, which represent a prominent component of large nerve bundles, composed of numerous, other, unlabeled axons and dendrites. Immunoreactive axons and terminals display multiple varicosities, filled with lucent spherical vesicles (40 nm average diameter), and are often in direct contact with unlabeled dendrites, presumed to arise from intrinsic pancreatic neurons. However, definitive synaptic contacts involving immunoreactive axon terminals were never observed, nor was CGRP immunoreactivity ever detected in neuronal cell bodies within intrapancreatic ganglia. Cellular immunoreactivity is relegated to perikarya at the peripheral margin of each islet of Langerhans, which emit one or more short, thick processes, which often terminate upon fenestrated capillaries. Immunoreaction product in these cells is concentrated in large secretory vesicles (∼230 nm diameter), which are dispersed throughout the somata and frequently appear to open into the perivascular space of capillaries. Immunoreactive axons, innervating the islets, are sparse and do not appear to have preferential association with immunoreactive cells. Present findings provide further evidence for a dual role of CGRP in pancreatic functions via a neuronal pathway and hormonal mechanisms.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Considerable differences exist among species in the patterns of regulation of pancreatic secretion. Although rabbit pancreas is quite often used for in vivo and in vitro studies of pancreatic function, responses of this gland in vivo to common pancreatic stimuli have never been characterised in detail. That was the purpose of this study. The data demonstrate the existence of a spontaneous fluid secretion that can be increased by intravenous infusions of secretion (sevenfold), cholecystokinin-octapeptide (CCK8) (threefold), and carbachol (sixfold). The electrolyte composition of the secretion evoked by each of these stimuli was similar: sodium and potassium concentrations were constant and slightly higher than those in plasma at all secretory rates, whereas bicarbonate concentration rose with secretory rate to approach a plateau of about 125 mmol/L, and chloride concentration fell to a plateau of about 35 mmol/L. In terms of protein secretion, secretin caused a small but significant rise in output, while CCK8 and carbachol evoked the expected large increase. Thus, regulation of pancreatic electrolyte secretion in rabbit differs from that in dog, cat, and human, on the one hand, and rat, on the other hand, and most closely resembles the pattern observed in guinea pig.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Perfusion of the main pancreatic duct in cats with a dilute solution of bile salts increases ductal permeability. Subsequent perfusion of a permeable duct with activated pancreatic enzymes results in acute edematous pancreatitis. Simultaneous infusion of 1616 dimethyl-PgE2converts edematous pancreatitis to acute hemorrhagic pancreatitis (AHP). AHP may be associated with a reduction in pancreatic blood flow; it is certainly associated with increases in micro vascular permeability. Low dose dopamine is a splanchnic vasodilator and may also reduce pancreatic microvascular permeability through beta agonist effects. In these studies, we investigated the effect of dopamine in an established feline model of biliary AHP. We also studied its effect on blood flow in both normal pancreas and after induction of AHP. We found that dopamine significantly reduced the degree of pancreatic inflammation, even when administered up to 12 h after onset of biliary AHP. However, the drug had no significant effect on blood flow either in normal pancreas or in the gland affected by hemorrhagic pancreatitis. We concluded that the effect of dopamine was most likely due to its ability to reduce pancreatic microvascular permeability.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Human pancreas contains two cholinesterase isoenzymes: acetyl-cholinesterase (AChE) and butyrylcholinesterase (BuChE). In the present study, binding potency of two organophosphates for human cholinesterases were compared by the Ellman method. Echothiophate was found to have much greater potency than iso-OMPA for both cholinesterases. Using Karnovsky histochemical stains on human pancreatic tissue, the same results were confirmed. Dose-response studies with acetylcholine were done on viable pancreas fragments from nine human donors, without pancreatic disease (group I). Cold-preservation time was less than 30 h. Pancreas was minced into fragments, after the technique of Scheele and Palade, placed in Eagle's medium, and gassed with 0. Amylase release was measured by the Phadebas Method and corrected for basal release. There was a dose-dependent response to acetylcholine at 1 and 2 h, with a shift in peak amylase release to the left, when fragments were preincubated in 10−4Mechothiophate. This indicated a 100-fold increase in sensitivity to acetylcholine. In three patients with chronic pancreatitis (Group 11), there were variable patterns of response of amylase release to acetylcholine, and higher basal outputs. In Group 111, prolonged storage conditions of over 40 h were tested for 4 pancreas donor tissues. There was no response to acetylcholine. These studies show that for up to 30 h cold storage, fragments of pancreas from human organ donors respond to acetylcholine in dose-dependent manner. An organophosphate, echothiophate (10−4M) which inhibits both cholinesterases, increases pancreatic sensitivity to acetylcholine, and these results are similar to findings from canine pancreas fragments, which also showed increased sensitivity.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Acute pancreatic oedema with hyperamylasaemia was induced in mice by subcutaneous administration of cholecystokinin octapeptide (CCK8). Comparison with effect of caerulein showed that cholecystokinin is less potent in vivo. To investigate the observed difference in response, threonine3CCKS and methionine5caerulein were synthesised and evaluated. Comparison of these peptides suggests that difference in bioactivity is related to possession of extra N-terminal residues rather than substitution of threonine for methionine.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We examined the effect of age on the trophic response of the pancreas to chronic treatment with cholecystokinin (CCK), bombesin, or pentagastrin. Three age groups (3-, 12-, and 24-months) male F344 rats received saline; CCK-8 (5 ng/kg), bombesin (10 μgkg), or pentagastrin (100 μg/kg) by intraperitoneal injection t.i.d. for 2 weeks. Rats were then killed and the pancreases excised, weighed, and assayed for DNA, RNA, protein, and polyamine (putrescine, spermidine, and spermine) concentrations and contents. We found that none of the treatments altered body weight at any age. All three hormones increased pancreas size and cell number in 3-month old rats, but by 12 months, all three had increased only pancreatic RNA content. Pancreatic spermidine concentration was decreased by all three hormone regimens in 3- but not in 12-month old rats, and pancreatic putrescine concentration and content were increased in 12-month old rats receiving all three hormones. There was no change in any parameter following any of the three hormones, tested at 24 months of age. We conclude that, at the dosages tested, the trophic response of pancreas to chronic administration of CCK, bombesin, and pentagastrin, which is normally present in young adult rats, is lost with aging.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The essential role of cholecystokinin (CCK) in pancreatic regeneration after pancreatitis or resection has been supposed, but not yet clearly demonstrated. In rats, 6–8 weeks after 60% distal resection of the pancreas a gradual increase in pancreatic weight and contents of DNA, protein, trypsin, chymotrypsin and amylase, occurred (there was no increase in lipase); Pancreatic regeneration stopped thereafter. Nonparallel increases in enzyme values were similar to those seen after CCK administration. Indeed, basal CCK levels increased significantly by the 6th week and declined thereafter. A one month S.C. administration of CCK-octapeptide (CCK-8) (3 × 300 ng/kg/d) accelerated regeneration in the first month, but it had almost no effect during the second or third postoperative months. A two week S.C. administration of a specific CCK antagonist, CR 1409 (3 × 4 mg/kg/d) totally prevented regeneration by the fifth and sixth weeks, but did not diminish pancreatic weight or DNA and protein contents during the first two weeks. Alcohol administration (12 g/kg/d) reduced CCK release and prevented pancreatic regeneration during the three-month experimental period. These data indicate that CCK has an essential role in pancreatic regeneration and that the deleterious effect of alcohol on regeneration involves inhibition of CCK release.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Pancreatic polypeptide and peptide YY are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests secondarily mediated mechanism(s) of action. To determine the role of extrinsic neural and intrinsic cholinergic elements on this inhibitory effect, a total of nine dogs underwent two-stage extrapancreatic denervation and creation of a chronic pancreatic fistula. After recovery, pancreatic polypeptide or peptide YY (400 pmol/kg/h) was administered during the intermediate hour of a 3-hour secretin (125 ng/kg/h)/cholecystokinin (50 ng/kg/h) infusion. Exocrine secretion during pancreatic polypeptide or peptide YY hours was compared with that of the first and third hours. The studies were then repeated during infusion of atropine (10 μg/kg/h). Despite extrinsic denervation, pancreatic polypeptide and peptide YY significantly inhibited secretinlcholecystokinin-induced pancreatic output. Although less profound, significant inhibition persisted in the presence of an atropine background. Pancreatic polypeptide or peptide YY infusion also decreased the exocrine response to meal stimulation. We conclude that the inhibitory effects of pancreatic polypeptide and peptide YY are not mediated by extrapancreatic, and possibly not by intrapancreatic cholinergic, neural pathways.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The purpose of this study was to examine the effect of transanal (intracolonic) infusion of bile acid on release of peptide YY (PYY) and cholecystokinin (CCK)-stimulated pancreatic exocrine secretion in seven conscious dogs. CCK-8 (50 ng/kg/h) was given intravenously for 120 min and either tau-rocholic acid (TA, 1 or 2 mmol/h) or saline was infused transanally (150 ml/h) during the 0–60-min period of CCK infusion. Transanal infusion of TA (1 or 2 mmol/h) significantly inhibited output of CCK-stimulated pancreatic protein, compared to transanal infusion of saline during the first 60 min. On the average, the magnitude of inhibition was ∼45%. Plasma concentrations of PYY increased significantly in response to intracolonic infusion of TA or saline. Transanal infusion of TA (1 or 2 mmol/h) significantly increased plasma levels of PYY when compared with transanal infusion of saline during the first 60 min. The magnitude of the increase of plasma PYY levels was −50 pg/ml (p< 0.05). Plasma levels of pancreatic polypeptide were not altered significantly by transanal infusion of TA. Our results suggest that release of endogenous PYY by TA in the colon plays a role in the inhibition of CCK-stimulated pancreatic exocrine secretion. Bile salts in the hindgut may participate in the physiologic regulation of pancreatic exocrine secretion by stimulation of release of ileal-colonic PYY.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Neuropeptide Y (NPY) is a unique 36 amino acid peptide with strong sequence homology to pancreatic polypeptide and peptide YY. In the rat pancreas, NPY-positive fibers have been demonstrated in close association with exocrine structures, suggesting a regulatory role for the peptide. In conscious rats with pancreatic ductal cannulas, amylase output stimulated by cholecystokinin octapeptide (CCK-8: 0.2 pg kg−1h−1was dose-dependently inhibited by intravenous NPY infusion (20,40, and 80 pg kg−1h−1). Inhibitory effects were rapid in onset but reversed with cessation of NPY infusion. With continuous NPY infusion (40 μg kg−1h−1), prolonged inhibition of amylase output by the vagal stimulant 2-deoxyglucose (100 mg kg−1) was observed (>50% inhibition in each of nine consecutive 10-min periods). In contrast, NPY infusion in doses of 20, 40, or 80 pg kg−1h−1produced no alteration in immunoreactive somatostatin levels. In vitro, NPY incubation (10−113-10−8M) produced no change in basal amylase release from dispersed, purified acinar cells. In addition, co-incubation of NPY (10−8-10−6M) with CCK-8 (10−13-10−5M) produced no inhibition of CCK-stimulated amylase release from dispersed acini. In contrast, NPY (10−6M) produced significant inhibition of amylase release from pancreatic lobules that had been stimulated by 75 μM potassium (135 ± 11% versus 177 ± 18% of basal level) or by 25 μM veratridine (196 ± 19% versus 398 ± 152%). NPY is a potent inhibitor of pancreatic exocrine secretion in the rat in vivo and in pancreatic lobules in vitro. The actions of NPY are exerted indirectly and do not involve circulating somatostatin. Inhibition of pancreatic neurotransmission may be involved in the actions of NPY on the exocrine pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID