Pancreatic polypeptide is not involved in the regulation of the migrating motor complex in man

The role of pancreatic polypeptide (PP) and motilin in the regulation of the migrating motor complex (MMC) was studied in normal subjects. Both plasma motilin and PP levels changed cyclically in the fasted state and were highest in the late phase II period preceding the activity front in the duodenum. A continental breakfast invariably disrupted the MMC and induced a fed pattern of motility. After the meal plasma motilin levels decreased whereas PP levels rose significantly. Infusion of pure porcine motilin during the fasted state induced an activity front and a rise in plasma PP levels. Infusion of bovine PP in doses producing plasma PP levels above the postprandial values neither induced an activity front nor prevented its occurrence. During PP infusion, however, plasma motilin levels were low, although the activity front was not inhibited. PP seems to have no clear role in the regulation of the motor component of the MMC of man. The role of motilin in the production of the activity front of the MMC is discussed.     

Variations in plasma motilin, somatostatin, and pancreatic polypeptide concentrations and the interdigestive myoelectric complex in dog

We have looked at the plasma concentrations of motilin, pancreatic polypeptide (PP), and somatostatin (STS) during the various phases of the interdigestive motor complex (IDMC) in dogs. As expected, motilin cyclical increase was always associated with the phase III of the IDMC. Statistical analysis of PP variations revealed a significant rise 10 min before duodenal phase III; however, in individual animals, this relationship was inconsistent. Although a dose-related increase in PP blood levels was induced by administration of synthetic canine motilin (0-200 ng kg-1 iv), fasting plasma levels of PP were not correlated with the concentrations of circulating endogenous motilin. After truncal vagotomy, while motilin release and the intestinal motility pattern remained unaltered, the phase III associated cyclical increases of PP disappeared. Infusion of physiological amounts of PP (1 microgram kg-1 h-1 for 3 h) mimicking the postprandial release failed to reproduce a fed pattern type of intestinal motility and of motilin secretion. No statistical correlation could be established between STS plasma levels and the motor activity of the intestine. STS plasma levels were not correlated with circulating concentrations of motilin and the exogenous administration of physiological doses of synthetic canine motilin failed to modify STS plasma levels. Morphine (200 micrograms kg-1 iv) stimulated only the release of motilin. These data suggest that the role played by circulating concentrations of PP and STS in the control of the IDMC in dog is at most minimal.     

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.     

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.     

Acid inhibition by intestinal nutrients mediated by CCK-A receptors but not plasma CCK

We examined the role of CCK-A receptors in acid inhibition by intestinal nutrients. Gastric acid and plasma CCK and gastrin levels were measured in rats with gastric and duodenal fistulas during intragastric 8% peptone and duodenal perfusion with saline, complete liquid diet (CLD; 20% carbohydrate, 6% fat, and 5% protein), and the individual components of CLD. Acid output was significantly inhibited (50-60%) by CLD, lipid, and dextrose. Plasma CCK was significantly increased by CLD (from 2.6 +/- 0.3 to 4.8 +/- 0.5 pM) and lipid (4.6 +/- 0.5 pM). CCK levels 50-fold higher (218 +/- 33 pM) were required to achieve similar acid inhibition by exogenous CCK-8 (10 nmol x kg(-1) x h(-1) iv). Intestinal soybean trypsin inhibitor elevated CCK (10.9 +/- 2.5 pM) without inhibiting acid secretion. The CCK-A antagonist MK-329 (1 mg/kg iv) reversed acid inhibition caused by CLD, lipid, and dextrose. Peptone-stimulated gastrin (21.7 +/- 1.9 pM) was significantly inhibited by CLD (14.5 +/- 3.6 pM), lipid (12.3 +/- 2.2 pM), and dextrose (11.9 +/- 1.5 pM). Lipid and carbohydrate inhibit acid secretion by activating CCK-A receptors but not by altering plasma CCK concentrations.     

Peripheral motilin administration stimulates feeding in fasted rats

Although the physiologic function of the gastrointestinal hormone motilin remains uncertain, plasma levels of this peptide vary with migrating myoelectric complexes (MMCs) in the small intestine. In the fed state, both MMCs and plasma motilin are suppressed. During fasting, cyclical peaks of motilin in plasma occur at the same time as Phase III of the MMC cycle occurs in the duodenum. This dependence of motilin concentrations in plasma on the feeding state of the animal prompted an investigation of the effects of motilin on feeding behavior. Intraperitoneal injection of motilin into fasted, but not fed, rats stimulated eating in a dose dependent manner. A significant stimulation of feeding was seen at doses of 5 and 10 μg/kg. Sated rats did not eat whether injected with motilin or vehicle. The feeding response to motilin was blocked by prior injection of the rats with naloxone, naltrexone, or pentagastrin. The dose response suppression of food intake by naloxone was similar in fasted animals treated with motilin or vehicle. Motilin may function as a hunger hormone during periods of fasting.     

5-羟色胺和胃动素在狗小肠移行性复合运动调控中的作用

应用慢性植入小肠腔外应力传感器记录清醒狗小肠移行性复合运动（ＭＭＣ）。在颈外静脉和支配１０￣１５ｃｍ肠段的空肠动脉内分别放置－硅胶管以备灌流药物的取血样品用。本研究观察了静脉和动脉注射药物对小肠ＭＭＣ的影响及ＭＭＣ不同时相血浆５－羟色胺（５－ＨＴ）和胃动素的浓度变化。结果表明：（１）ＭＭＣ不同时相血浆５－ＨＴ和胃动素浓度呈周期性变化,５－ＨＴ峰值在胃动素峰值之前出现。血浆５－ＨＴ浓度在ＭＭＣⅡ相后     

Achlorhydria induced changes in gastrin, somatostatin, H+/K(+)-ATPase and carbonic anhydrase in the sheep.

Gastrin, somatostatin, H+/K(+)-ATPase and carbonic anhydrase are principal elements of acid secretion. We investigated in the conscious sheep the effect of 24 h omeprazole (an H+/K(+)-ATPase inhibitor) infusion on these elements at the level of synthesis, storage and secretion. Omeprazole inhibited acid secretion-pH increased from 3.0 to 7.1 at 24 h. Plasma amidated and glycine extended gastrin increased 3-fold while the ratio of amidated to glycine extended gastrins (4:1) remained unchanged. Despite the increase in circulating gastrin, antral gastrin concentration and mRNA did not change significantly. Gastrin-17 (amidated and glycine extended) was the predominant form in the circulation and antrum, although there were preferential increases in larger forms following omeprazole treatment. Omeprazole had no effect on somatostatin mRNA or peptide levels in the fundus. Similarly, plasma somatostatin remained unchanged. However, antral somatostatin increased significantly (63%) following omeprazole treatment accompanied by a 4-fold increase in its mRNA. Fundic H+/K(+)-ATPase mRNA was unchanged but a significant increase (87%) in carbonic anhydrase II mRNA was observed. Omeprazole induced hypergastrinaemia occurred without a measurable reduction in storage or increased synthesis of gastrin at 24 h. Increased antral somatostatin synthesis and storage may result from stimulation by plasma gastrin on antral D cells, independent of acid. The rise in carbonic anhydrase II mRNA in the absence of any change in H+/K(+)-ATPase mRNA may reflect the differential sensitivity of the genes encoding these two enzymes to the stimulatory action of gastrin.     

The activity front of the migrating motor complex of the human stomach but not of the small intestine is motilin-dependent

The role of motilin in the generation of the gastric component of phase 3 of the migrating myoelectric complex (MMC) was studied in human volunteers. Interdigestive motor activity was recorded manometrically in five normal subjects after a fast of at least 15 h. Intraluminal pressures were measured in the gastric antrum at 4 levels 3 cm apart and in the upper small bowel at 3 levels 25 cm apart. Blood samples were drawn every 10 min for radioimmunoassay of motilin and PP. After 2 spontaneously occurring activity fronts (AF) had been recorded, bovine PP was infused intravenously at a rate of 50 μg/h. Following the third AF a combination of PP (50 μg/h) and 13-norleucine-motilin (30 μg/h) was infused until after the next AF. It was found that 90% of the spontaneous AFs originated in the stomach. They were preceded by a motilin peak. During the PP infusion, plasma PP levels increased from 29 to 256 pmol/l, motilin decreased from 42 to 15 pmol/l, and all AFs originated in the small bowel. During the combined PP and motilin infusion, plasma motilin increased to 330 pmol/l, and all AFs again originated in the stomach. It is concluded that motilin has an important role in the regulation of the MMC activity front in the stomach, but not in the small intestine. Postprandial rises in plasma PP might be involved in lowering motilin levels after a meal, and indirectly, in the disruption of gastric MMCs during digestion.     

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.     

Lipids, proteins and carbohydrates stimulate the secretion of intestinal cholecystokinin in the pig

Food intake enhances the release of intestinal cholecystokinin (CCK) in the pig but the contribution of individual nutrients to the CCK response has not yet been established in this species. Six hogs (mean weight 50 kg) were fitted with a duodenal fistula for instillation of nutrients and with portal (PV) and carotid (CA) catheters for blood sampling. After a 24-h fast, the animals received 1,000 ml of isotonic solution containing 440 kcal of carbohydrate (starch hydrolysate), or of protein (casein hydrolysate) or fat (Intralipid) or a control saline solution by 60-min intraduodenal perfusion after a 60-min control period during which the animals received saline. Portal and peripheral blood samples were collected at 15-min intervals for CCK radioimmunoassay. Intraduodenal perfusion of fat provoked a sharp increase in CCK-Like immunoreactivity (CCK-LI) in PV (peak 76.6 +/- 12.2 pM from basal 10.8 +/- 1.2 pM) and in peripheral blood (peak 46.7 +/- 8.4 pM from basal 9.1 +/- 1.0 pM). The protein hydrolysate induced a transient increase in plasma CCK-LI during the first 30 min of intestinal perfusion (PV: peak 40.1 +/- 5.0 pM from basal 11.9 +/- 1.4 pM; CA: 31.8 +/- 4.0 pM from basal 8.5 +/- 0.8 pM). The transient effect of proteins on CCK release might reflect the consequence of somatostatin release from intestinal stores. Starch hydrolysate promptly raised plasma CCK-LI level to a plateau value (PV: 52.5 +/- 13.1 pM from basal 11.9 +/- 1.4 pM; CA: 35.4 +/- 8.0 from basal 8.5 +/- 0.8 pM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pancreatic and gut hormones during fasting: insulin, glucagon, and somatostatin

When adult male rats were fasted for 24 or 72 h there was no change in the pancreatic content of insulin or glucagon, but the somatostatin content increased at 72 h. This contrasts with earlier reports of reduced pancreatic somatostatin after fasting. After a 48-hour fast there was an increase in the concentration of duodenal somatostatin, and a tendency toward reduced concentrations in stomach, jejunum, and ileum. When duodenal mucosa and muscle extracts were chromatographed the relative amounts of putative somatostatin-28 and somatostatin-14 were unchanged. Insulin secretion from the perfused pancreata of 72-hour-fasted rats was markedly reduced, but glucagon and somatostatin secretion was indistinguishable from that of fed controls. These results indicate that in spite of the marked alterations of nutrient metabolism and insulin secretion which occur during fasting, the pancreatic content of insulin, glucagon and somatostatin and the gut concentration of somatostatin are well maintained.     

Metabolic and hormonal response to short term fasting after endurance training in the rat

The metabolic and hormonal response to short term fasting was studied after endurance exercise training. Rats were kept running on a motor driven rodent treadmill 5 days/wk for periods up to 1 h/day for 6 wk. Trained and untrained rats were then fasted for 24 h and 48 h. Liver and muscle glycogen, blood glucose, lactate, beta OH butyrate, glycerol, plasma insulin, testosterone and corticosterone were measured in fed and fasted trained and untrained rats. 48 h fasted trained rats show a lower level of blood lactate (1.08 +/- 0.05 vs 1.33 +/- 0.08 mmol/l-1 of blood glycerol (1 +/- 0.11 vs 0.84 +/- 0.08 mmol/l-1), and of muscle glycogen. There is a significant increase in plasma corticosterone in 48 h fasted trained rats from fed values. Plasma testosterone decreases during fasting, the values are higher in trained rats. Plasma insulin decreases during fasting without any difference between the two groups. These results show higher lipolysis, and decreased glycogenolysis in trained animals during 48 h fasting. The difference between the groups in steroid hormone response could reduce neoglucogenesis and muscle proteolysis in trained animals.     

Do motilin and pancreatic polypeptide regulate duodenal bile acid delivery?

The plasma levels of the enteric hormones, motilin and pancreatic polypeptide, cycle in association with fasting intestinal motility and are altered by feeding. Intravenous administration of motilin causes gallbladder contraction and increased sphincter of Oddi phasic motor activity, whereas pancreatic polypeptide causes gallbladder relaxation. To determine if endogenous plasma levels of motilin and pancreatic polypeptide control sphincter of Oddi and gallbladder motility, and regulate duodenal bile acid delivery, we measured during fasting and after feeding the correlation between (a) changes in plasma motilin or pancreatic polypeptide, and (b) the duodenal delivery of a steady-state hepatic output of radiolabelled bile acid. Four dogs were prepared with duodenal cannulas. Duodenal motility was recorded manometrically. Plasma levels of pancreatic polypeptide and motilin were determined during a full cycle of the migrating myoelectric complex for 20 min before and 40 min after ingestion of a standard meal. To assess the effect of the sphincter of Oddi and the gallbladder together, or the gallbladder alone on duodenal bile acid delivery, the dogs received a continuous i.v. infusion of [14C]taurocholic acid (TCA); duodenal delivery of TCA was quantitated with the sphincter of Oddi intact using duodenal marker perfusion, or with the sphincter of Oddi cannulated and zero outflow resistance. In the interdigestive period with the sphincter of Oddi intact, only 0.1 (r2) of the variance of duodenal bile acid delivery can be predicted from the variance of motilin, and the correlation of plasma pancreatic polypeptide with duodenal TCA delivery is opposite that expected if pancreatic polypeptide caused gallbladder relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral administration of somatostatin reduces postprandial plasma triglycerides, gastrin and gut glucagon-like immunoreactivity.

The present study was designed to determine if orally administered somatostatin can reduce the postprandial rise in plasma triglycerides, gastrin, gut glucagon-like immunoreactivity (GLI) and the pancreatic hormones insulin and glucagon. Ten overnight fasted dogs were fed a fat-protein meal with or without 2 mg synthetic somatostatin, followed by another 2 mg somatostatin 90 min later. After the meal with somatostatin, postprandial plasma triglyceride levels were significantly lower for 5 hours, GLI levels for 3.5 hours and gastrin levels for 1 hour compared to the controls. Plasma insulin, glucagon and somatostatin-like immunoreactivity was not different from the control experiments. It is concluded that orally administered somatostatin lowers the postprandial levels of triglycerides, GLI and gastrin in dogs. This may have therapeutic implications for the management of gastrointestinal and metabolic disorders.     

Effect of moderate incremental exercise, performed in fed and fasted state on cardio-respiratory variables and leptin and ghrelin concentrations in young healthy men.

BACKGROUND: Although hormonal responses to exercise performed in fed state are well documented, far less in known about the effect of a single exercise bout, performed after overnight fasting, on cardio-respiratory responses and hormones secretion. It has been reported that recently discovered hormones as leptin and ghrelin may affect cardiovascular responses at rest. However, their effect on the cardiovascular responses to exercise is unknown. AIMS: This study was designed to determine the effect of overnight fasting on cardio- respiratory responses during moderate incremental exercise. We have hypothesised that fasting / exercise induced changes in plasma leptin / ghrelin concentrations may influence cardiovascular response. MATERIAL AND METHODS: Eight healthy non-smoking men (means +/- SE.: age 23.0 +/- 0.5 years; body mass 71.9 +/- 1.5 kg; height 179.1 +/- 0.8 cm; BMI 22.42 +/- 0.49 kg x m(-2) with VO2max of 3.71 +/- 0.10 l x min(-1)) volunteered for this study. The subjects performed twice an incremental exercise test, with the increase of power output by 30 W every 3 minutes. Tests were performed in a random order: once in the feed state--cycling until exhaustion and second, about one week later, after overnight fasting--cycling until reaching 150 W. RESULTS: In the present study we have compared the results obtained during incremental exercise performed only up to 150 W (59 +/- 2 % of VO2max) both in fed and fasted state. Heart rate measured during exercise at each power output, performed in fasted state was by about 10 bt x min(-1) (p = 0.02) lower then in fed subjects. Respiratory quotient and plasma lactate concentration in fasted state were also significantly (p<0.001) lower than in the fed state. Pre-exercise plasma leptin and ghrelin concentrations were not significantly different in fed and fasted state. Exercise induced increase in hGH was not accompanied by a significant changes in the studied gut hormones such as ghrelin, leptin, and insulin, except for plasma gastrin concentration, which was significantly (p = 0.008) lower in fasting subjects at the power output of 150 W. Plasma [IL-6] at rest before exercise performed in fasted state was significantly (p = 0.03) elevated in relation to the fed state. This was accompanied by significantly higher (p = 0.047) plasma noradrenaline concentration. Plasma IL-6 concentration at rest in fed subjects was negatively correlated with plasma ghrelin concentration (r = -0.73, p < 0.05) and positively correlated with plasma insulin concentration (r = 0.78, p < 0.05). Significant negative correlation (r = -0.90; p < 0.05) was found between plasma insulin and ghrelin concentration at rest in fed subjects. CONCLUSIONS: We have concluded that plasma leptin and ghrelin concentrations have no significant effect on the fasting-induced attenuation of heart rate during exercise. We have postulated that this effect is caused by increased plasma norepinephrine concentration, leading to the increase in systemic vascular resistance and baroreceptor mediated vagal stimulation. Moreover we believe, that the fasting-induced significant increase in plasma IL-6 concentration at rest, accompanied by higher plasma norepinephrine concentration and lower RQ, belongs to the physiological responses, maintaining energy homeostasis in the fasting state.     

Motilin release by intravenous infusion of nutrients and somatostatin in conscious dogs

to investigate the regulatory mechanism of motilin release, plasma motilin was measured by radioimmunoassay in healthy dogs during the fasting state and after intravenous administration of various nutrients and somatostatin. The fasting plasma motilin levels of these dogs were found to fluctuate intermittently. Intravenous glucose loading lowered plasma motilin, but immediately after the end of the glucose infusion as abrupt rise of plasma motilin was observed. Mixed amino acids administered intravenously abruptly inhibited motilin secretion, and plasma motilin levels remained low even 45 min after the end of the infusion. On the other hand, no remarkable change in plasma motilin was noted after the fat infusion. Following somatostatin infusion, plasma motilin was significantly decreased, remaining low even 30 min after the end of the infusion. These observations led us to conclude than motilin secretion is regulated by somatostatin and by nutrients coming through intravenous routes.     

Influence of acute exposure to high altitude on Basal and postprandial plasma levels of gastroenteropancreatic peptides

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O₂-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated ( = area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.     

Somatostatin inhibits bombesin-induced effects on migrating myoelectric complexes in the small intestine of the rat

The effect of i.v. infusions of bombesin and somatostatin, administered either separately or in combination, on migrating myoelectric complexes (MMCs) in the small intestine were studied in conscious, fasted rats. The myoelectrical activity was recorded by means of three bipolar electrodes chronically implanted into the duodenum and jejunum. Infusion of bombesin (0.5, 0.9 and 3 pmol . kg-1 . min-1) interrupted the MMC and induced irregular spiking activity similar to that observed on feeding. Only after the highest dose a consistent inhibition of the MMCs and a significant increase (P less than 0.05) of the spiking activity were achieved at all recording levels. Somatostatin (90 pmol . kg-1 . min-1) did not interrupt the MMC, but reduced significantly the incidence of the activity fronts and spiking activity of the MMCs (P less than 0.05). The effects of bombesin (3 pmol . kg-1 . min-1) on the MMC pattern were inhibited by simultaneous infusion of somatostatin (P less than 0.05). In a second series of experiments, using anesthetized rats, infusion of bombesin (0.5 and 3 pmol . kg-1 . min-1) increased the plasma concentration of neurotensin- gastrin-like immunoreactivities in a dose-dependent manner. The results show that bombesin alters the myoelectrical activity of the small intestine from a fasting to a fed pattern. Since the effect of bombesin was inhibited by the hormone release inhibitor somatostatin, it is suggested that the effect of bombesin on MMC may be secondary to the release of gastrointestinal peptides, such as neurotensin or gastrin.     

Effect of exercise on the pancreatic polypeptide response to food in man

Modest elevations in pancreatic polypeptide (PP) have been observed during exercise while fasting. To determine whether the PP response to a meal is similarly affected by exercise, seven healthy subjects were studied on two occasions. First, the postprandial PP response was determined during rest and then compared to a meal which was subsequently followed by a 45 min period of moderate exercise. Postprandial exercise significantly (P less than 0.01) enhanced the plasma PP response to peak levels of 182 +/- 22 pM versus 85 +/- 22 pM at rest. Concomitantly the plasma glucose fell to a nadir of 84 +/- 4 mg/dl which was significantly (P less than 0.01) below the rest level of 129 +/- 8 mg/dl. Although the rise in PP paralleled the fall in glucose, there was little relationship (r = 0.27) between the incremental changes in these two parameters. Thus, exercise is a natural setting which augments the plasma PP response to a meal. The mechanism may be related to the enhanced cholinergic vagal activity associated with the attendant fall in glycemia.