Interdigestive Pancreatic Secretion Research Articles

Circadian coupling between pancreatic secretion and intestinal motility in humans.

Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.

Effect of Helicobacter pylori Infection on Gastrointestinal Motility, Pancreatic Secretion and Hormone Release in Asymptomatic Humans

Background: Helicobacter pylori infection is associated with complex alterations of the gastric physiology in patients with ulcer disease or functional dyspepsia. We aimed at evaluating whether H. pylori infection is accompanied by changes in interdigestive and postprandial gastrointestinal motility, exocrine pancreatic secretion or hormone release in asymptomatic subjects. Methods: Nineteen healthy men (age range 26-35 years) were studied after 12 h fasting. Motor activity was recorded for a complete motor migrating complex cycle and two postprandial hours. Pancreatic enzyme secretion was evaluated using a standard duodenal perfusion technique. Plasma concentrations of gastrin, PP and motilin were determined at 15-min intervals. H. pylori infection was proved by serology and 13C-urea breath test. Results: Eight subjects (42%) were H. pylori positive. Interdigestive and postprandial gastrointestinal motility were similar in H. pylori positive and negative subjects. Interdigestive pancreatic secretion was increased in H. pylori positive subjects ( P < 0.05). Postprandial pancreatic secretion tended also to be higher in H. pylori positive subjects. H. pylori infection was associated with an increased postprandial release of gastrin ( P < 0.05) as well as with a slight increase of interdigestive gastrin release. The release of PP and motilin, as well as the interdigestive coordination between gastrointestinal motility, pancreatic secretion and hormone release, was not altered by H. pylori infection. Conclusions: H. pylori infection in asymptomatic subjects is associated with changes not only in gastric physiology but also in pancreatic function. This first reported link between H. pylori and the pancreas could have pathophysiological implications in pancreatic diseases and therefore deserves further study.

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.

Effects of intraduodenal administration of tarazepide on pancreatic secretion and duodenal EMG in neonatal calves

The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and the mechanism(s) involved in CCK-induced pancreatic secretion were studied in conscious calves. Seven 1-week-old calves were fitted with a pancreatic duct catheter, duodenal cannula and duodenal electrodes. Pancreatic exocrine secretion and duodenal EMG were studied following intraduodenal CCK-A receptor antagonist (Tarazepide), intravenous atropine, and intravenous or intraduodenal CCK-8 administrations. Tarazepide decreased duodenal electric activity, reduced interdigestive pancreatic secretion, especially protein; reduced cephalic and early postprandial (milk) induced secretion of bicarbonate and protein. Pancreatic protein secretion to intravenous CCK-8 was little affected by atropine, but was significantly reduced by Tarazepide±atropine; in contrast, protein secretion to intraduodenal CCK-8 was abolished by Tarazepide or atropine. We conclude that pre- and especially early postprandial pancreatic secretion are partly controlled via CCK-A (mainly mucosal) mediated mechanisms.

Role of pancreaticoduodenal neural connections in coordination of interdigestive upper gut motility and pancreatic secretion

Role of pancreaticoduodenal neural connections in coordination of interdigestive upper gut motility and pancreatic secretion

Effect of L364 718 on interdigestive pancreatic exocrine secretion and gastroduodenal motility in conscious sheep

The present study examined roles of endogenous cholecystokinin (CCK) and CCK-A receptors in the regulation of pancreatic exocrine secretion and gastroduodenal motility in conscious sheep during interdigestive period. Interdigestive exocrine secretion of ovine pancreas changed cyclically corresponding with cycle of duodenal migrating myoelectric complexes (MMC). During second phase of the duodenal MMC, intravenous injection of L364 718 at 2.45 μmol kg −1 inhibited exogenous CCK-8-induced pancreatic exocrine secretion. Intravenous infusion of the antagonist at 2.45 μmol kg −1/5 min for 5 min also inhibited significantly the pancreatic enzyme secretion without CCK-stimulation to half of that in the control, but not the fluid and bicarbonate secretion. Atropine infusion (i.v.) at 72.0 nmol kg −1/5 min significantly inhibited not only enzyme but also fluid and bicarbonate secretion. Corresponding to the inhibition of the exocrine secretion, L364 718 induced premature phase III in duodenal electromyogram (EMG) in three of the five sheep. Omasal EMG was inhibited slightly but significantly by L364 718, however, neither regular ruminal contractions nor abomasal EMG were altered by L364 718. In contrast, the atropine infusion inhibited only amplitude of ruminal contractions. These results suggest that endogenous CCK contributes to the regulation of interdigestive pancreatic exocrine secretion, omasal contractions and duodenal MMC in the ovine gastrointestinal tract via CCK-A receptors.

Role of endogenous CCK in regulation of interdigestive pancreatic exocrine secretion in sheep (Ovis aries)

The role of endogenous cholecystokinin (CCK) in the regulation of pancreatic exocrine secretion during the interdigestive period was studied in conscious sheep. Intravenous infusion of proglumide (15, 30 and 60 mumol/kg/min) for 70 min significantly decreased flow rate, protein and amylase output in pancreatic juice by 80% at the maximum dose, as well as atropine (10 micrograms/kg/min), without a significant decrease in plasma concentration of immunoreactive CCK. Intravenous injection of CCK (114 pmol/kg) increased the pancreatic secretion during atropine infusion, but not during proglumide infusion. These results suggest that the regulation of interdigestive pancreatic exocrine secretion in sheep depends greatly on endogenous CCK as well as on the cholinergic mechanism.

Exocrine pancreatic function in the early phase of human acute pancreatitis.

Little is known about exocrine pancreatic function during human acute pancreatitis. We aimed to evaluate interdigestive exocrine pancreatic secretion and pancreatic polypeptide (PP) release during the early phase of acute pancreatitis in humans. Eight patients with acute pancreatitis (six biliary, one alcoholic, and one idiopathic acute pancreatitis) were studied within 72 h from the onset of symptoms. Four patients had necrotizing and four had edematous acute pancreatitis. Normal values were obtained from 26 normal subjects matched by sex and age. Interdigestive pancreatic secretion was studied by a duodenal intubation perfusion technique. Enzyme output was calculated for consecutive 15-min periods over 3-4 h and expressed as units per hour within a secretion cycle and units per hour around a secretion peak. Plasma PP concentrations were measured by radioimmunoassay in 15-min intervals. All variables studied were similar in patients with acute pancreatitis and in controls. PP release in acute pancreatitis was maintained in a normal cyclical pattern closely related to the secretory cycles. Interdigestive exocrine pancreatic secretion in the early phase of mild to moderate acute pancreatitis in humans remains within the normal range. This finding provides a rational basis for early therapeutic inhibition of pancreatic secretion in human acute pancreatitis.

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates exocrine pancreas in conscious preruminating calves

The effects of new hypothalamic peptides, PACAP-27 and PACAP-38, and secretin and VIP on the interdigestive pancreatic secretion and duodenal myoelectric activity during the asecretory phase of the pancreatic interdigestive cycle, compared with the milk ingestion phase, were examined in five calves. Peptides were infused for 5 min into the external jugular vein (0, 3, 10, 30 and 100 pmol/kg body wt during the asecretory phase of the pancreatic interdigestive cycle, and the pancreatic secretory response was compared with that obtained during milk ingestion. Intravenous infusion of PACAP-27 caused dose-related stimulation of pancreatic juice flow and bicarbonate and protein output; this effect was identical to infusion of secretin. The effect of PACAP-38 was less pronounced, and that of VIP was the weakest. Pancreatic juice volume and bicarbonate responses during milk ingestion were similar to responses obtained with the highest doses of hypothalamic peptides and secretin, whereas postprandial protein secretion was much greater than the secretion stimulated with peptides. It was concluded that PACAP from the VIP/secretin family may stimulate pancreatic exocrine secretion in conscious calves and a part of the pancreatic response to food intake can be mediated by PACAP.

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates exocrine pancreas in conscious preruminating calves

The effects of new hypothalamic peptides, PACAP-27 and PACAP-38, and secretin and VIP on the interdigestive pancreatic secretion and duodenal myoelectric activity during the asecretory phase of the pancreatic interdigestive cycle, compared with the milk ingestion phase, were examined in five calves. Peptides were infused for 5 min into the external jugular vein (0, 3, 10, 30 and 100 pmol/kg body wt during the asecretory phase of the pancreatic interdigestive cycle, and the pancreatic secretory response was compared with that obtained during milk ingestion. Intravenous infusion of PACAP-27 caused dose-related stimulation of pancreatic juice flow and bicarbonate and protein output; this effect was identical to infusion of secretin. The effect of PACAP-38 was less pronounced, and that of VIP was the weakest. Pancreatic juice volume and bicarbonate responses during milk ingestion were similar to responses obtained with the highest doses of hypothalamic peptides and secretin, whereas postprandial protein secretion was much greater than the secretion stimulated with peptides. It was concluded that PACAP from the VIP/secretin family may stimulate pancreatic exocrine secretion in conscious calves and a part of the pancreatic response to food intake can be mediated by PACAP.

Local versus peripheral blood administration of cholecystokinin-8 and secretin on pancreatic secretion in calves.

The effects of local and peripheral administration of cholecystokinin-8 (CCK-8) and secretin on the interdigestive pancreatic secretion were examined in conscious preruminating calves. Six calves were surgically fitted with a pancreatic catheter and duodenal cannula, duodenal electrodes and strain gauges, and cooling devices on the cervical vagi. Local intra-arterial (I.A.) infusions were made into the duodenal branch of the right gastroepiploic artery, and peripheral infusions (I.V.) into the external jugular vein. CCK-8 and secretin were infused I.A. and I.V. for 5 min (0, 10, 30 and 100 pmol (kg body weight)-1) during the asecretory phase of the pancreatic interdigestive cycle. CCK-8 and secretin at 100 pmol kg-1 were administered concomitant with reversible cold vagal blockade. Local infusion of CCK-8 without vagal blockade resulted in a significantly faster and stronger pancreatic response than the respective peripheral infusion, although CCK in peripheral blood plasma was paradoxically only minimally increased after I.A. CCK-8 in comparison with a marked increase after I.V. CCK-8. Vagal blockade noticeably decreased the pancreatic response for I.A. CCK-8, but not for I.V. CCK-8. Secretin produced similar pancreatic responses after I.V. and I.A. administration, but the plasma secretin concentration in peripheral blood was markedly lower after I.A. than after I.V. infusions. Cold vagal blockade uniformly reduced the stimulatory effect of I.A. and I.V. secretin infusion on the exocrine pancreas. In calves, CCK-8 apparently stimulates the exocrine pancreas by two different mechanisms: by a direct effect that is vagally independent as well as by an indirect effect in the duodenum that is vagally dependent. The indirect effect of secretin in the duodenum is less clear, but both direct and indirect effects of secretin depend on vagal integrity.

Periodic fluctuations in pancreatic secretion and duodenal motility investigated in neonatal calves.

To clarify the relative timing of clinical changes in duodenal motility and pancreatic secretion in newborn calves, we recorded duodenal electrical and mechanical activity and analysed pancreatic secretion and migrating myoelectric complex (MMC). In eight calves integrated recordings were derived from sites near the duodenal bulb and pancreatic accessory duct orifice, and pancreatic juice was sampled after an overnight fast, after a feed, and during reversible cold vagal blockade. Peak secretion coincided with duodenal irregular spiking activity and the nadir with absence of spiking. Feeding elicited electrical and mechanical hyperactivity in the duodenum, dissipated the MMC temporarily, and dramatically increased the juice volume and bicarbonate and protein outputs. Periodic fluctuations in secretion started shortly after a feed, as did recovery of the duodenal myoelectric complexes. Cold vagal blockade reversibly disrupted the synchronous changes in duodenal motility and pancreatic secretory activity, though the close association was not totally obliterated. In milk-fed calves interdigestive pancreatic secretion apparently rises and falls in phase with migrating myoelectric complexes of the proximal duodenum and the vagus is largely, though not exclusively, responsible for co-ordinating these changes.

Cholinergic regulation of phase II interdigestive pancreatic secretion in humans.

Small fluctuations in cholinergic input may be involved in the regulation of human interdigestive pancreatic secretion. To determine the effects of small changes in cholinergic tone on phase II interdigestive trypsin secretion, we gave cholinergic agonists or antagonists to 17 healthy fasting subjects who underwent gastrointestinal intubation. Duodenal trypsin outputs, gastroduodenal motility, and plasma levels of pancreatic polypeptide (PP) as a marker of cholinergic tone were measured during intravenous infusion of bethanechol (0, 5, or 40 micrograms.kg-1.h-1) or atropine (0, 4, or 16 micrograms.kg-1.h-1) given during phase II alone or in combination based on a 3 x 3 factorial design. Data were evaluated by a response surface analysis of the average log values for the test period (using the average of log values of the control period as a covariate). Bethanechol increased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) within the ranges of spontaneous fluctuations of trypsin output and PP during phase II, but did not disrupt the periodicity of pancreatic secretion or the characteristic cyclical pattern of interdigestive motility and induction of phase III activity. Atropine markedly decreased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) and abolished the cycling of interdigestive pancreatic secretion and motor activity. These data suggest the hypothesis that cholinergic pathways participate in the control of interdigestive pancreatic secretion during phase II, while enzyme secretion during phase III may be regulated by other mechanisms.

The Inhibitory Effect of Octreotide on Exocrine Pancreatic Secretion in Conscious Dogs

The effects of somatostatin and its analogue, octreotide (SMS201-995), on pancreatic secretion and gastroduodenal motility in response to secretin and cholecystokinin octapeptide (CCK-8) were studied in five conscious dogs. Intravenous infusions of octreotide or somatostatin (1 nmol kg-1 h-1) inhibited periodic pancreatic secretion and the potentiation of fluid and bicarbonate responses to secretin at 60 ng kg-1 h-1 associated with the interdigestive gastroduodenal motility peaks (migrating motor complex). Pancreatic fluid and bicarbonate responses to secretin (125-1,000 ng kg-1 h-1) were not inhibited by octreotide or somatostatin. Pancreatic protein and enzyme responses to secretin and CCK-8 at 50 and 100, but not at 200 and 400, ng kg-1 h-1 were inhibited by octreotide and somatostatin. These inhibitory effects were similar to those of atropine (25 micrograms kg-1 h-1). The inhibition of protein responses to CCK-8 (100 ng kg-1 h-1) was dependent on octreotide dose. It is concluded that both octreotide and somatostatin, like atropine, inhibit interdigestive pancreatic secretion and the responses to small, but not large, doses of secretin and CCK-8 in conscious dogs.

Adrenergic modulation of interdigestive pancreatic secretion in humans

Whether the adrenergic pathways participate in the control of interdigestive pancreatic function in humans is uncertain. To determine if changes in α-or β-adrenergic tone modulate interdigestive pancreatic enzyme output, 16 healthy subjects were intubated with an orojejunal tube to collect and quantify pancreatic trypsin secretion and record motility. After observation of a complete interdigestive cycle (control period), eight groups of two subjects each received 2-hour intravenous infusions of the α- and β-agonist epinephrine (50 ng · kg−1 · min−1), the α-antagonist phentolamine (5 mg/2 min followed by 500 μg/min), the β-antagonist propranolol (5 mg/2 min followed by 80 μg/min), or saline as control, alone or in combination. Drugs were assigned in a random mode according to a 23 factorial design. Analysis of variance showed that epinephrine decreased trypsin output by 43% (P < 0.05). By contrast, trypsin output was increased fourfold in the presence of phentolamine (P < 0.01), whereas propranolol had no effect. These data suggest that an inhibitory α-adrenergic tone modulates human interdigestive pancreatic enzyme secretion whereas β inputs are less important.

Cyclic interdigestive pancreatic exocrine secretion: Is it mediated by neural or hormonal mechanisms?

Cyclic interdigestive exocrine pancreatic secretion and duodenal motility are closely linked. However, the mechanisms controlling this association are not well understood. The aim of this study was to determine whether a neural or hormonal mechanism controls the temporal association of interdigestive secretion and duodenal motility. In five dogs, the pancreas was autotransplanted to the pelvis with anastomosis of the pancreatic duct orifice to the bladder. Electrodes were positioned to monitor motility patterns of the in situ duodenum. After 10 days, dogs were studied on four occasions during fasting. Pancreatic output of amylase activity continued to cycle, but the periodicity of enzyme peaks (mean ± SE) was different from the period of the duodenal migrating motor complex (MMC) (60 ± 3 vs. 125 ± 7 minutes; P < 0.05). When grouped according to phase of duodenal MMC, amylase output per 10 minutes during phase I was significantly less than the outputs during phase II or III (135 ± 52, 214 ± 78, and 228 ± 73 × 103 U; P < 0.05). However, there was no temporal relationship of the cyclic output of amylase to duodenal phase III. No differences were found when amylase output was analyzed for the 30 minutes before phase III compared with the 30 minutes after phase III (687 ± 253 vs. 378 ± 110 × 103 U; P > 0.05). Plasma motilin concentrations varied with duodenal MMC, but no relationship existed between plasma motilin or plasma pancreatic polypeptide and peaks in amylase output. This study suggests that the close temporal coordination of interdigestive pancreatic exocrine secretion and duodenal motility is controlled primarily by a neural mechanism.

Cyclic interdigestive pancreatic exocrine secretion: Is it mediated by neural or hormonal mechanisms?

Cyclic interdigestive exocrine pancreatic secretion and duodenal motility are closely linked. However, the mechanisms controlling this association are not well understood. The aim of this study was to determine whether a neural or hormonal mechanism controls the temporal association of interdigestive secretion and duodenal motility. In five dogs, the pancreas was autotransplanted to the pelvis with anastomosis of the pancreatic duct orifice to the bladder. Electrodes were positioned to monitor motility patterns of the in situ duodenum. After 10 days, dogs were studied on four occasions during fasting. Pancreatic output of amylase activity continued to cycle, but the periodicity of enzyme peaks (mean +/- SE) was different from the period of the duodenal migrating motor complex (MMC) (60 +/- 3 vs. 125 +/- 7 minutes; P less than 0.05). When grouped according to phase of duodenal MMC, amylase output per 10 minutes during phase I was significantly less than the outputs during phase II or III (135 +/- 52, 214 +/- 78, and 228 +/- 73 x 10(3) U; P less than 0.05). However, there was no temporal relationship of the cyclic output of amylase to duodenal phase III. No differences were found when amylase output was analyzed for the 30 minutes before phase III compared with the 30 minutes after phase III (687 +/- 253 vs. 378 +/- 110 x 10(3) U; P greater than 0.05). Plasma motilin concentrations varied with duodenal MMC, but no relationship existed between plasma motilin or plasma pancreatic polypeptide and peaks in amylase output. This study suggests that the close temporal coordination of interdigestive pancreatic exocrine secretion and duodenal motility is controlled primarily by a neural mechanism. (Gastroenterology 1992 Apr;102(4 Pt 1):1378-84)

Role of Secretin in Basal and Fat-Stimulated Pancreatic Secretion in Conscious Rats*

The role of endogenous secretin in basal and fat-stimulated pancreatic exocrine secretion was investigated in conscious rats. Rats were prepared with chronic fistulas draining bile and pancreatic juice, which was collected and returned to the duodenum at all times. Six days postoperative rats were fasted overnight, and pancreatic protein and fluid secretion were monitored for 3 h under basal conditions (0.15 M NaCl, intraduodenally) and during 2 h of intraduodenal infusion of a 20% triglyceride emulsion (Liposyn). Solutions were infused at 4.6 ml/h. Rats received a single bolus injection of 0.1 ml antisecretin serum or normal rabbit serum starting in the second hour of the basal period, and the effect on basal and fat-stimulated pancreatic protein and fluid secretion was determined. Antisecretin serum significantly inhibited basal interdigestive pancreatic protein and fluid secretion by 43% and 36%, respectively. Infusion of 20% fat emulsion stimulated a 2.1-fold increase in pancreatic protein and fluid secretion. The stimulation of both protein and fluid secretion was significantly inhibited by 60% by antisecretin serum. Plasma secretin after 2 h of fat infusion was 17.7 +/- 1.8 pM and was greatly reduced by the presence of secretin antiserum. The results support the hypothesis that secretin released by fatty acids is an important mediator of the pancreatic protein and fluid secretory response to dietary fat in the rat.

Control of interdigestive and intraduodenal meal-stimulated pancreatic secretion in rats

Mechanisms of neural (vagal and cholinergic) and hormonal [cholecystokinin (CCK)] control of pancreatic exocrine secretion were studied in basal interdigestive conditions and after stimulation by an intraduodenal meal in rats equipped with a semichronic pancreatic fistula. Bile was recirculated into the duodenum, and a solution of trypsin and electrolytes was continuously infused. Pancreatic secretion was compared in control experiments, after vagotomy, and after venous infusion of cholinergic and CCK antagonists. Basal pancreatic secretion was decreased by atropine, pirenzepine, and hexamethonium and to a lesser extent by vagotomy (protein output decreased more than fluid and HCO3- outputs). The CCK antagonists L364,718 and lorglumide had no effect on basal interdigestive pancreatic secretion. Small doses of atropine (8 and 25 micrograms.kg-1.h-1) did not modify the cumulated pancreatic response to the meal, whereas larger doses (75 and 225 micrograms.kg-1.h-1) increased it by 40-85%, according to the variables. Pirenzepine and hexamethonium did not modify the pancreatic response. Vagotomy had no effect on fluid and HCO3- responses and tended to increase protein response. L364,718 and lorglumide completely inhibited the protein response and decreased the fluid and HCO3- responses by 75 and 40%, respectively. L364,718 also suppressed the increased pancreatic response induced by atropine. This work confirms the prominent role of neural cholinergic mechanisms in the control of basal interdigestive pancreatic secretion in rats. In contrast, the pancreatic protein response to an intraduodenal meal depends on CCK, whereas fluid and HCO3- responses also depend on other hormonal factors. Our results suggest that a muscarinic (probably M3) mechanism can decrease the postprandial CCK release independently of the pancreatic feedback control by trypsin.

Role of pancreatic polypeptide in the regulation of pancreatic exocrine secretion in dogs.

The effect of intravenous infusion of synthetic human pancreatic polypeptide (HPP) or a rabbit anti-PP serum on pancreatic exocrine secretion was studied in 10 dogs with gastric and Thomas duodenal cannulas. The infusion of HPP, at a dose of 1 microgram.kg-1.h-1, achieved a plasma PP concentration that mimicked the peak plasma concentration of PP in both interdigestive and postprandial states. This dose of HPP significantly inhibited pancreatic secretion in the interdigestive state. By contrast, immunoneutralization of circulating PP by a rabbit anti-PP serum resulted in significant increases (P less than 0.05) in both interdigestive and postprandial pancreatic secretion, including water, bicarbonate, and protein. The increase in the pancreatic secretion paralleled a decrease in circulating PP level, which lasted for as long as 5 days. Furthermore, the anti-PP serum blocked the inhibitory action of exogenous HPP on pancreatic exocrine secretion. The present study indicates that endogenous PP plays a significant role in the regulation of the pancreatic exocrine secretion in both interdigestive and digestive states. Thus we conclude that PP is another hormone regulating pancreatic exocrine secretion in dogs.