Variations of plasma immunoreactive motilin, pancreatic polypeptide, gastrin and somatostatin along the duodenal motility cycle in the pig

The peripheral plasma concentrations of immunoreactive motilin, pancreatic polypeptide (PP), somatostatin and gastrin were measured in 7 pigs fasted to 24 h and subsequently fed a standard meal. Plasma motilin peaked during the last part of phase II activity of the migrating myoelectric complex (MMC) sequence (25.2 +/- 2.3 pM), the lowest value being recorded during phase I (10.6 +/- 1.5 pM) after a 24 h fast. Plasma motilin remained at a low level during the digestive pattern of duodenal activity, no fluctuation occurring when the first postprandial MMC recurred. At variance analysis, gastrin and PP were not released phasically with MMC in the fasting state, while at autocovariance both peptides tended to fluctuate during the MMC sequence with positive and negative peaks at regular intervals along MMC cycles. No variation of plasma somatostatin was observed in the fasting animals. These findings argue against a major role of circulating PP, gastrin and somatostatin-like components in the control of fasted and post absorptive duodenal motility in pigs while the role of motilin remains equivocal.     

Effect of atropine and somatostatin on bombesin-stimulated plasma gastrin,cholecystokinin and pancreatic polypeptide in man

Infusion of the neuropeptide bombesin stimulates the secretion of several gastrointestinal hormones by an unknown mechanism. We have investigated the effects of atropine (15 ng/kg as bolus followed by 2.5 ng/kg · 30 min) and somatostatin (125 μg as i.v. bolus followed by 62.5 μg/30 min) on the stimulation of 3 hormones (gastrin, cholecystokinin and pancreatic polypeptide) by 60 pmol/kg · 20 min bombesin in 6 healthy volunteers. Plasma samples for measurement of hormones by sensitive and specific radioimmunoassays were obtained at − 5, 0, 2.5, 5, 7.5, 10, 15, 20, 25 and 30 min. Bombesin induced significant increases in plasma gastrin (12 ± 2 to 34 ± 3 pM; P < 0.0005), cholecystokinin (1.2 ± 0.2 to 8.9 ± 0.7 pM; P < 0.0001) and pancreatic polypeptide (22 ± 4 to 72 ± 19 pM; P < 0.05). There were great differences between the effects of atropine and somatostatin on the hormonal responses to bombesin. Atropine slightly increased the response of gastrin by 19% and that of cholecystokinin by 15%, but strongly inhibited the bombesin-stimulated pancreatic polypeptide secretion by 97%. On the other hand, somatostatin inhibited the bombesin-induced secretion of gastrin by 48%, cholecystokinin by 82% and pancreatic polypeptide by 107%. These results point to considerable qualitative and quantitative differences in the stimulatory mechanisms of bombesin on the hormones studied.     

Decreased plasma motilin concentrations in pregnancy.

Plasma motilin concentrations were measured in 37 women during the second and third trimester of pregnancy and one week after delivery. The mean plasma motilin concentrations, both fasting and after a glucose load and a mixed meal, were significantly (p less than 0.001) reduced during pregnancy, returning to the normal range one week post partum. Pregnancy appears to have a profound inhibitory effect on plasma motilin, and this may in part be responsible for the gastrointestinal hypomotility associated with pregnancy.     

Gastrin, motilin and pancreatic polypeptide levels after two different parenteral regimens in infants

We studied the effect of 2 different parenteral regimens upon gastrin, motilin and pancreatic polypeptide (PP) levels in infants. In 15 children, aged 1-25 months, plasma peptide levels were measured by radioimmunoassay in the fasting state and after a 2-h infusion of either a mixture of amino acids, glucose and lipids (A) or a mixture of amino acids and glucose (B) only. Wide interindividual fluctuations were noted, especially for motilin and PP, but, except for PP, intraindividual fluctuations were low. Indeed, a good correlation was found, not only between the 2 pre-infusion levels, but also between pre- and postinfusion levels in both experiments. In fact for all 3 peptides, pre- and postinfusion levels differed only slightly and non-significantly. We conclude that during parenteral feeding levels of motilin, PP and gastrin remain practically unchanged and are not influenced by the addition of lipids. In addition, during the observation period basal levels did not change, indicating that the mechanisms regulating basal secretion were not affected.     

Changes in plasma glucagon, pancreatic polypeptide and insulin during development of alloxan diabetes mellitus in dog

Changes in canine plasma glucose, immunoreactive glucagon (IRG), pancreatic polypeptide (PP) and insulin (IRI) were studied during the acute development of diabetes mellitus after iv alloxan injection. 100 mg or 75 mg/kg body weight of alloxan was injected iv and blood was taken successively till one or two days later. Plasma glucose showed four phases: first immediate and moderate decrease appeared 30 min after injection, second initial hyperglycemic phase, third hypoglycemic and fourth diabetic ones. Plasma IRI had already increased to 182 +/- 60 microU/ml 10 min after injection and again began to increase after about 6 h, peaking to 134 +/- 49 microU/ml at 18 h. Plasma IRG began increasing gradually soon after alloxan injection. The initial value was 196 +/- 26 pg/ml and it increased to 534 +/- 144 pg/ml at 4 h during the initial hyperglycemic phase, then reached a higher level through the hypoglycemic and diabetic phases. The change in plasma PP was similar to that in IRG. The initial value was 256 +/- 95 pg/ml at 12 h after injection, peaking to 840 +/- 100 pg/ml in the hypoglycemic phase. Similar blunted values were obtained following 75 mg/kg alloxan injection. Thus not only plasma IRI but also plasma IRG and PP varied greatly during the acute development of alloxan diabetes and some contribution of IRG to the initial hyperglycemic phase was suggested.     

Effect of physiological increments of blood glucose on plasma somatostatin and pancreatic polypeptide levels in dogs

The present study was designed to determine the effects of physiological increments of plasma glucose levels upon basal and stimulated plasma somatostatin and pancreatic polypeptide levels. In seven conscious dogs the elevation of plasma glucose levels by 30-40 mg/dl did not change basal somatostatin and pancreatic polypeptide levels. During stimulation of these two hormones by acetylcholine and the octapeptide of cholecystokinin intravenous infusion of glucose elicited a significant decrease of somatostatin levels by 30 pg/ml and of pancreatic polypeptide levels by 300 pg/ml. The present data demonstrate that a physiological elevation of plasma glucose levels inhibits stimulated but not basal somatostatin and pancreatic polypeptide levels which may be of importance for nutrient entry and metabolism.     

Relationship between intravenous ethanol, alcohol-induced inhibition of pancreatic secretion and plasma concentration of immunoreactive pancreatic polypeptide, vasoactive intestinal peptide, and somatostatin in man

We have studied in seven men, consuming less than 50 g alcohol daily, the effect of intravenous (i.v.) ethanol on (a) hormonally (secretin + CCK PZ) submaximally stimulated pancreatic secretion and (b) blood levels of pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and somatostatin. After intravenous ethanol (600 mg/kg), pancreatic secretion decreased in all subjects and plasma levels of PP and VIP increased significantly. Moreover, there was a significant correlation between the mean inhibition of chymotrypsin output and the mean increase in PP plasma levels during the first 45 min following ethanol infusion. Therefore i.v. infusion of alcohol elicits release of PP and VIP and PP release could explain in part at least the alcohol-induced pancreatic inhibition observed in non-alcoholic men.     

Insulin, glucagon, pancreatic polypeptide hormone and somatostatin in the goat pancreas: demonstration by immunocytochemistry

Insulin, glucagon, pancreatic polypeptide hormone (PP) and somatostatin immunoreactive cells were demonstrated in the islet of the goat pancreas by the immunofluorescence procedure. Islet cells showing immunostaining for the hormones appeared to have a characteristic distribution. The demonstration of PP and somatostatin within the pancreas of the goat suggests they may be significant in modulating intra- and extra-islet function in this ruminant species.     

Ontogeny of cells containing insulin, glucagon, pancreatic polypeptide hormone and somatostatin in the bovine pancreas

Antibodies to insulin, glucagon, pancreatic polypeptide hormone (PP) and somatostatin were used in the immunofluorescence histochemical procedure to study the ontogeny of pancreatic endocrine cells containing the four hormones in the bovine fetus of approximately 100 days gestation to term. Pancreatic sections from the bovine neonate and adult were also examined for the cellular distribution of the four hormones. Immunoreactive cells staining for insulin, glucagon, PP and somatostatin were present in the pancreas of all fetuses studied. Each endocrine cell type displayed a characteristic distribution within the developing pancreas and in the neonate and adult. The presence of the four islet hormones relatively early in bovine fetal life suggests that they may be important in intra- and extra-islet metabolism in the fetus.     

Suppression of somatostatin levels in the hepatic portal and systemic plasma of the rat by synthetic human pancreatic polypeptide.

The 1:1 Cu(II), Co(II), Co(II)-O₂, Fe(II)-NO, and Fe(III) complexes of depBLM have been investigated by ESR spectroscopy and compared with the corresponding metal complexes of BLM. DepBLM which lacks the α-amino group of β-aminoalanine portion in BLM molecule, forms the metal complexes different from BLM with regard to the fifth axial donor. In addition, the formation of hydroxyl radical by the depBLM-Fe(II) complex is remarkably lower than that by the BLM-Fe(II) complex. This study indicates an important effect of fifth axial nitrogen on metal coordination and oxygen activation of BLM.     

The effect of somatostatin and 16,16-dimethyl-prostaglandin E2 on bombesin-stimulated canine gastric acid, plasma gastrin and pancreatic polypeptide secretion

We studied the effect of the intravenous infusion of 16,16-dimethylprostaglandin E2 methyl ester (di-M-PGE2) and somatostatin on bombesin-stimulated gastric acid secretion, plasma gastrin and plasma pancreatic polypeptide in four chronic gastric fistula dogs. Bombesin-stimulated gastric acid secretion was significantly inhibited by somatostatin and virtually abolished by di-M-PGE2. Both agents caused significant, but indistinguishable inhibition of gastrin release (P less than 0.05). Bombesin-stimulated pancreatic polypeptide release was also significantly inhibited by both somatostatin and di-M-PGE2; the inhibitory effect of somatostatin was significantly greater than that of di-M-PGE2 (P less than 0.05). This study provides further evidence in support of the complex interrelationships between agents responsible for the modulation of gastrointestinal physiology.     

Relationship of postprandial motilin, gastrin, and pancreatic polypeptide release to intestinal motility during vagal interruption.

Experiments were performed to determine how postprandial motilin, gastrin, and pancreatic polypeptide plasma concentrations measured during vagal blockade relate to coincident small intestinal motility patterns. Feeding produced a postprandial pattern of intestinal motility coincident with a sustained increase in gastrin and pancreatic polypeptide and a decline in motilin plasma concentrations. Vagal blockade replaced the fed pattern with one similar to migrating motor complex (MMC) activity. Highest motilin plasma concentrations were observed during phase III of this MMC-like activity, as occurs in the fasted state. Vagal blockade reduced but did not abolish the postprandial increase in plasma gastrin and pancreatic polypeptide concentrations. Termination of vagal cooling produced a decline in motilin and an elevation in gastrin and pancreatic polypeptide concentrations, coincident with the return of the fed pattern. In conclusion, during vagal blockade in the fed state (i) motilin, but not gastrin or pancreatic polypeptide plasma concentrations, fluctuate with the MMC-like activity, and any measurement of motilin concentration under these circumstances must be interpreted on the basis of gut motility patterns, and (ii) gastrin and pancreatic polypeptide concentrations are marginally elevated, but these changes are not enough to disrupt the MMC or have any motor effect. Lastly, the fed pattern and the postprandial changes in motilin, gastrin, and pancreatic polypeptide concentrations are in part dependent upon intact vagal pathways.     

Effects of pancreastatin on insulin and pancreatic polypeptide secretion in the dog

Porcine pancreastatin (1.19 nmol) was administered into the peripheral vein (i.v.) or the third cerebral ventricle (i.t.v.) of dogs and its effect on the secretion of insulin and pancreatic polypeptide (PP) studied. Neither means of administration had any effect on basal and glucose-induced insulin or PP secretion. However, i.v. pancreastatin did inhibit the i.v. CCK-8-induced insulin but not PP release. Pancreastatin may thus play a role in the regulation of insulin secretion in the canine pancreas.     

Effect of electrical stimulation of the vagus on plasma motilin concentration in dog

Ten dogs anesthetized with α-chloralose were prepared with platinum monopolar electrodes in the antrum, duodenum and jejunum to record myoelectrical activity and bipolar stimulating electrodes placed on distal cut end of both cervical vagi to apply electric stimulation. Blood samples were obtained from both portal and femoral veins before and after bilateral vagal stimulation was initiated while the myoelectric activity was recorded continuously. The stimulation parameters used were low frequency (9V, 5 cps, 0.5 ms) and high frequency stimulus (9V, 30 cps, 10 ms) for 10 min. During the stimulation, plasma motilin concentrations increased significantly in both portal and femoral veins with simultaneous increases in the spike activity. The increment in the motilin level of portal venous blood was more marked. In 7 dogs, high frequency stimulation was repeated while the animals received i.v. atropine, 100 μg/kg-hr. Atropinization completely blocked the increase in the motilin concentration in response to high frequency stimulus with a simultaneous inhibition of the spike activity. The study suggests strongly that the vagus nerve plays an important role on endogenous release of motilin through its cholinergic pathway.     

Effect of proglumide, a cholecystokinin receptor antagonist, on caerulein-stimulated pancreatic enzyme secretion and pancreatic polypeptide release in the dog

In five conscious dogs we studied the effect of proglumide, a cholecystokinin (CCK) antagonist, on caerulein-stimulated pancreatic secretion and release of pancreatic polypeptide (PP). Graded doses of caerulein (15-240 ng/kg per h) were infused intravenously. Experiments were repeated with a fixed infusion of proglumide (40 mg/kg per h). Release of PP following increasing doses of caerulein was significantly inhibited by proglumide (P less than 0.01). However, proglumide did not significantly affect caerulein-stimulated pancreatic protein secretion. Proglumide might be useful in defining the physiological role of CCK.     

Patterns of immunoreactive pancreatic polypeptide in human plasma

Pancreatic polypeptide (PP) is synthesized as an amino-terminal moiety of a precursor peptide and is released into plasma during stimulation as an amidated hormone (PP1-36). The purpose of this investigation was to ascertain the immunoreactive forms of PP in human plasma using HPLC chromatographic technique. Plasma was obtained from five normal volunteers under various postprandial intervals and from the Blood Bank. PP in each plasma sample was processed for HPLC analysis by immunoprecipitation and/or immunoaffinity extractions. Migration patterns of PP-forms were identified under isocratic elution. This study shows that human plasma contains four distinct immunoreactive (IR) forms of PP during stimulation by a protein-rich meal. These forms are PP1-36 (peak 4), PP3-36 (peak 3) and unidentified material migrating as peak 2 and peak 1. The corresponding migration constants were Kav 0.828 +/- 0.04, Kav 0.790 +/- 0.003, Kav 0.570 +/- 0.009 and Kav 0.409 +/- 0.007, respectively. The predominant fasting from of IR PP chromatographed as peak 1, while peaks 2 and 4 were reduced in amplitude. The 1 h and 3 h postprandial chromatograms of HPLC profiles of plasma PP were similar in shape but lower in relative magnitude and amplitude. The authenticity of peak 4 as the migration of native PP1-36 was confirmed using purified IR native PP1-36 extracted from human pancreas. Partial amino acid sequence analysis of PP peak 3 revealed deletions of two N-terminal amino acid residues. The chemical identities of peaks 1 and 2 are unknown but appear to differ from PP in peaks 3 and 4 by virtue of their migration profiles. It is concluded that there are at least four distinct IR forms of PP in human plasma. Native PP1-36 accounts for less than 1% of total PP after an overnight fast and is about 1/3 of total postprandial IR plasma PP. Discernment of the nature and etiology of forms of PP in plasma may provide a new understanding of the role of PP in mammalian physiology.     

Somatostatin and the interdigestive migrating motor complex in man

The relationship between somatostatin and the interdigestive migrating motility complex (MMC) was determined in human volunteers. Motor activity was monitored manometrically by means of seven perfused catheters: four in the stomach, one in the duodenum, two in the jejunum. Blood samples were drawn every 10 min and radioimmunoassayed for motilin, pancreatic polypeptide and somatostatin. In four volunteers two activity fronts (AF) were recorded and somatostatin levels correlated to the manometric data. The start of an AF in the upper duodenum was accompanied by somatostatin peaks. Peak values, taken as the mean of the levels in the sample obtained after the start of an AF, the preceding sample and the next one, averaged 32 +/- 4 pM compared to 12 +/- 2 pM in the remaining period. In four volunteers somatostatin was infused in doses of 1.2, 2.4 and 4.8 pM/kg per min over three consecutive periods of 90 min, causing dose-dependent increments in plasma somatostatin levels of 7, 32 and 76 pM. In all volunteers and for all doses all gastric activity was completely inhibited. In the intestine phase 2 was abolished but phase 3 stimulated: during somatostatin infusion phase 3 occurred with an interval of 39 +/- 6 min. Motilin and PP levels were decreased. As the two lowest infusion doses caused increases in somatostatin levels that might be considered as physiological, somatostatin seems to have a physiological role in the regulation of the migrating motor complex. We propose that it facilitates the progressing of the activity front into the small intestine.     

Effects of human atrial natriuretic polypeptide on pancreatic exocrine secretion in the dog

We examined the effects of atrial natriuretic polypeptide (hANP) on exocrine function in the isolated and blood-perfused dog pancreas in situ. Intra-arterial injection of hANP (1-10 micrograms) resulted in the dose-dependent increases of the pancreatic juice secretion. The secretory activity of 3 micrograms of hANP was approximately equal to one third of the secretory activity of 0.1 units of secretin. The use of hANP increased the concentration of bicarbonate but not that of sodium and protein in the pancreatic juice as compared with the basal values. These secretory responses to hANP were not inhibited by treatment with haloperidol, sulpiride, phentolamine, propranolol, atropine, cimetidine or ethacrynic acid. These results suggest that hANP acts directly on the pancreatic exocrine gland to stimulate pancreatic secretion; without, however, increasing sodium excretion. The mechanism of this effect remains to be elucidated.