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T L Peeters

Publications and source records attributed to T L Peeters.

At least 91 records · Page 5Linked to original sources
PubMed1988

Comparison of motilin binding to crude homogenates of human and canine gastrointestinal smooth muscle tissue.

Pharmacological studies indicate that in man and in rabbit, but not in dog, motilin has a direct influence upon gastrointestinal smooth muscle. In accordance with this hypothesis we have presented direct biochemical evidence for the presence of motilin receptors on rabbit smooth muscle tissue. We have now extended our studies to human and canine tissue. Tissue homogenates were studied in binding experiments with iodinated porcine [Leu13]motilin and iodinated canine motilin. It was ascertained that the iodination procedure had little effect on the biological activity of the porcine analogue. In the human antrum specific binding of the iodinated porcine analogue was only found in the smooth muscle layer. It was absent in mucosal or serosal preparations. At 30 degrees C and pH 8.0, binding was maximal after 60 min of incubation, and was reversed by the addition of unlabeled porcine motilin. Binding was enhanced in the presence of calcium and magnesium ions. At a concentration of 10 mM MgCl2, binding was 220% of the binding observed in its absence. Displacement studies with synthetic porcine [Leu13]motilin or synthetic natural porcine motilin indicated a dissociation constant (Kd) of 3.6 +/- 1.6 nM and a maximal binding capacity (Bmax) of 77 +/- 9 fmol per mg protein. Canine motilin displaced iodinated porcine motilin with an apparent Kd of 2.2 +/- 0.9 nM. Compared to antral binding, receptor density decreased aborally and orally, and was absent in jejunum and ileum. In dog specific binding could not be demonstrated in antral and duodenal tissue, neither with labeled porcine nor with labeled canine motilin. However, labeled canine motilin was equipotent to labeled porcine motilin in binding studies with human tissue: the dissociation constant was 0.9 +/- 0.6 nM. The present studies therefore demonstrate the existence of a specific motilin receptor in the antroduodenal region of the human gut. Apparently, such receptors are not present in the canine gut. Our data support the hypothesis that in the human gastrointestinal tract, the gastroduodenal area is motilin's target region.

Animals↗
PubMed1988

SMS 201-995 prevents postprandial blood pressure reduction in normotensive and hypertensive elderly subjects.

The mechanism of postprandial blood pressure reduction in the elderly is unknown but it has been suggested that insulin and/or vasoactive gut hormones play a role in this phenomenon. The increase in insulin and other gut hormones induced by the glucose loading can be blocked by a synthetic long-acting somatostatin analogue. SMS 201-995. We carried out a double-blind randomized study on the effects of SMS 201-995 on the responses of blood pressure, heart rate, insulin and plasma noradrenaline to oral glucose loading in normotensive and hypertensive elderly subjects. After placebo was administered, mean arterial pressure fell by 15 +/- 1 mmHg (P less than 0.001) in hypertensive elderly and by 7 +/- 2 mmHg (P less than 0.01) in normotensive elderly subjects. In contrast, when SMS 201-995 was administered, blood pressure remained essentially unchanged in both groups. These data indicate that treatment with SMS 201-995 might be of value in patients with symptomatic postprandial hypotension.

Aged↗
PubMed1988

Effect of the long-acting somatostatin analogue SMS 201-995 on small-intestinal interdigestive motility in the dog.

The long-acting somatostatin analogue SMS 201-995, also called Sandostatin, is used in the treatment of acromegaly and peptide-secreting tumors. Little is known about its effect on gut motility, although such an effect might be expected considering the spectrum of activities of its parent molecule, somatostatin. We have studied the effect on the interdigestive motility of intravenous boluses of 0, 0.1, 0.5, 1.5, and 5.0 micrograms/kg of this analogue in 10 dogs with bipolar electrodes implanted along the entire small bowel. All doses induced, within 5 min of administration, premature phase-3 activity that was isolated to one segment, normally progressive, or simultaneous (stationary) in all channels. Only low doses induced isolated phase 3, whereas the frequency of the induction of stationary phase 3 increased with higher doses. In the next cycle of the migrating motor complex the duration of phase 1 was increased, although the duration of the whole cycle was not changed. This cycle ended with mostly ectopic phase-3 activity. During phase 2 of the following cycle ultra-rapid rushes of spiking activity progressing at a speed of 25 +/- 3 cm/sec in the upper jejunum were regularly observed. Although this pattern occurs very rarely under control conditions, it was present in 20%, 80%, and 100% of the experiments after doses of 0.5, 1.5, and 5.0 micrograms/kg, respectively. We conclude that gastrointestinal side effects observed during administration of SMS 201-995 might be related to these motility effects, which warrant further investigation. SMS 201-995 may be a tool to study the mechanism of the induction of ultra-rapid rushes and of stationary phase 3.

Animals↗
PubMed1988

Local nerve blockade by tetrodotoxin induces ectopic phase 3 of the migrating myoelectric complex in dogs.

The effect on the migrating myoelectric complex (MMC) of local nerve blockade in the jejunum was studied in five unanesthetized dogs. A silastic catheter was implanted in a terminal branch of a jejunal artery, perfusing a 5- to 10-cm segment, 45 cm below the ligament of Treitz. Small-bowel motor activity was studied electromyographically with implanted electrodes. Three different doses of tetrodotoxin (166, 333, 500 ng/kg/h) were administered intra-arterially for 5 h. During the 333- and 500-ng but not during the 166-ng/kg/h perfusions ectopic activity fronts started just below the perfused segment. At this time no phase-3 activity was observed in the proximal bowel. In addition to ectopic fronts normal MMCs were observed during the perfusions. These observations show that local nerve blockade induces phase-3 activity, probably by inhibiting an inhibitory nerve action.

Animals↗
PubMed1988

Interdigestive motility and motilin in hypophysectomized patients.

Basal fluctuations of motilin and their correlation to intestinal motor activity were studied in five hypophysectomized (anterior lobe resection) patients. A cyclic pattern of motor activity identical to the one described in normal volunteers was observed. The mean interval between two activity fronts (AF) was 115 min, which is not significantly different from the normal length. Motilin levels were within the normal range, and fluctuations correlated with the occurrence of an AF. The mean difference between motilin levels 15 min before the AF and at the time of the start of the AF was +15 pM (P less than 0.05). For the levels 15 min after the AF the mean difference was -9 pM (P less than 0.05). These values correlate well with those reported by us in normal volunteers, in whom the mean differences were +11 pM and -14 pM, respectively. It is concluded that the adenohypophysis is not involved in the regulation of motilin levels or in the regulation of interdigestive motility in man.

Digestion↗
PubMed1988

[Effect of liver bile on interdigestive electric activity of the stomach and small intestine in dogs].

Utilizing the chronic experimental dog model the effect of intraduodenal administration of bile upon the interdigestive electric activity of the stomach and small intestine was examined. For this purpose the functional cholecystectomy was performed and common bile duct was cannulated with two catheters. Tubes connected over the skin allowed spontaneous bile circulation during control experiments and in between the experimental periods. Nine pairs of electrodes were implanted into the stomach and small intestinal wall for electromyography. During other experiments standard bile was infused intraduodenally at the rate 0.5 ml.min-1 for 300 min and whole hepatic bile was introduced at the rates 2 ml.min-1 for 60 min and 30 ml.min-1 for 2 min. Hepatic bile infusion at the low rate, when started during phase II of the migrating myoelectric complex, induced the premature phase III after 10 +/- 2 min and caused about 20% reduction of cycle duration in the duodenum as compared to control experiments (P less than 0.05). Fast administration of hepatic bile elicited the premature phase III in 8 +/- 2 min, caused 20-30% reduction of the duodeno-jejunal cycle duration (P less than 0.05) in comparison with control group and induced in 26% phase III in the stomach. Cycles were shortened at the expense of markedly decreased duration of phase I; for example in the duodenum phase I was reduced from 30 +/- 3 (control experiments) to 11 +/- 2 min, P less than 0.001. Standard bile infusion exerted less pronounced changes, apart from increasing the propagation velocity of phase III in the first jejunal segment from 6 +/- 0.5 cm.min-1 in control group to 13 +/- 3 cm.min-1, P less than 0.05. In two experiments rapid bile administration evoked an inhibitory response. Results obtained suggest that the luminal bile stimulates the interdigestive electrical activity of the stomach and small bowel of the dog. This stimulatory effect may represent the feedback mechanism preventing the prolonged retention of continuously inflowing bile in a bowel section and, particularly, in the duodenum.

Action Potentials↗
PubMed1987

Increased plasma motilin concentrations in small cell carcinoma of the lung.

Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear.

Adult↗
PubMed1987

In man, only activity fronts that originate in the stomach correlate with motilin peaks.

We have tested the hypothesis that the imperfect correlation between the occurrence of plasma motilin peaks and the migrating motor complex (MMC) is related to the site of origin of the MMC. Gastric and small-intestinal motor activity was recorded manometrically in 16 normal subjects after an overnight fast. Blood samples were taken every 10 min and assayed for motilin. Fifty MMCs were recorded: 29 (58%) originated in the antrum and 21 (42%) in the small intestine. For gastric MMCs a motilin peak (45 +/- 5 pM) was found 10 min before the occurrence of the MMC in the duodenum. For intestinal MMCs no peak could be demonstrated. On an individual basis 27 of the 29 gastric activity fronts were associated with a motilin peak, versus 5 out of 21 intestinal MMCs. It is concluded that in man only gastric activity fronts are associated with plasma motilin peaks. Apparently, motilin is only involved in the regulation of the MMCs originating from the stomach.

Adult↗
PubMed1987

Interdigestive fluctuations of plasma bile acid concentration: relation to interdigestive motility pattern.

In the fasting state, delivery of bile acids into the duodenum is related to the interdigestive migrating motor complex (MMC) and occurs during late phase 2. It has also been shown that in the dog this secretion is transported to the ileum, where bile acids are reabsorbed. We therefore studied plasma bile acid and motilin concentration in relation to small intestinal motility in human volunteers. Motor activity was recorded manometrically in 5 normal subjects after an overnight fast, until at least one full cycle of the migrating complex had been recorded. Pressures were measured in the antrum at 4 levels and in the upper small bowel at 3 levels. Blood samples were drawn every 10 min for radioimmunoassay of motilin and conjugated bile acids. Motilin levels fluctuated in accordance with the MMC cycle. Bile acid levels also fluctuated, but although fluctuations were poorly correlated to motilin levels, peaks of plasma bile acid occurred at or around the time of phase 3 activity. Also, the time lags between bile acid peaks, motilin peaks and phase 3 activity were almost identical, suggesting that peaks of plasma bile acid concentration are due to the arrival and absorption in the ileum of bile acids secreted during the preceding phase 2 and transported by the preceding phase 3. The poor correlation of plasma bile acid peaks with motilin peaks is probably due to the variability of transport and absorption of bile acids.

Adult↗
PubMed1986

Pancreatic secretion in man with subclinical vitamin D deficiency.

The effects of subclinical vitamin D deficiency and vitamin D supplementation on oral glucose tolerance and secretion of pancreatic hormones were studied in 10 diphenylhydantoin-treated epileptic patients and 15 geriatric patients. Their mean serum concentrations of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 decreased markedly, but returned to normal within 2 weeks of oral supplementation with 25-hydroxyvitamin D3. The serum concentration of ionized calcium was within the normal range before treatment, and remained unchanged. Serum parathyroid hormone was increased during vitamin D deficiency, but decreased significantly (p less than 0.05) afterwards. In vitamin D-deficient epileptic and geriatric patients, the 2- and 3-h insulin levels after glucose ingestion were increased when compared with control values, and glucagon secretion was not suppressed by glucose. Oral glucose tolerance of both groups of patients did not change after 25-hydroxyvitamin D3 supplementation. Insulin secretion remained unchanged in geriatric patients, but was reduced to normal values in epileptic patients. Glucagon suppressibility by glucose was partly restored after vitamin D supplementation in epileptic patients but not in geriatric patients. In contrast to that observed in severely vitamin D-deficient rats or rabbits, correction of subclinical vitamin D deficiency failed to enhance insulin secretion or to improve glucose tolerance in man.

Age Factors↗
PubMed1986

Effects of corticotropin-releasing factor on plasma motilin and somatostatin levels and gastrointestinal motility in dogs.

The effects of intracerebroventricular and intravenous administration of corticotropin-releasing factor (CRF) on gastrointestinal motility, motilin-induced gastric motor response, and plasma motilin and somatostatin levels were investigated in fasted dogs chronically prepared with strain gauge transducers on the antrum and proximal jejunum. Administered intracerebroventricularly at doses of 20 and 100 ng/kg in fasted dogs, CRF suppressed for 4-5 h the gastric cyclic migrating motor complex. A similar dose (100 ng/kg) administered intravenously was inactive. Corticotropin-releasing factor administration by the intravenous route at 100 ng/kg did not alter the cyclic plasma motilin and somatostatin variations associated with the cyclic gastric motor events. During the blockade of antral migrating motor complex induced by intracerebroventricular administration of CRF, cyclic peaks of plasma motilin were absent whereas those of somatostatin persisted. The gastrointestinal migrating motor complex induced by the intravenous administration of porcine motilin (0.25 microgram/kg) was abolished when motilin was injected 2 h after the intravenous administration of CRF (100 ng/kg), whereas a similar dose of CRF administered intracerebroventricularly did not abolish the antral and jejunal motor responses to motilin. It is concluded that in fasted dogs, CRF administered centrally affects the interdigestive gastric motility and the release of motilin but not that of somatostatin. These results also suggest that the intracerebroventricular CRF-induced blockade of motilin release is responsible for the inhibition of gastric migrating motor complex and circulating CRF is able to affect the gastric motor response to porcine motilin through a peripheral mechanism that does not involve somatostatin and motilin secretion.

Animals↗
PubMed1986

Motilin receptors in rabbit stomach and small intestine.

Motilin receptors in rabbit antral and duodenal smooth muscle tissue were characterized by direct binding technique using 125I-labeled porcine motilin as a tracer ligand. Binding at 30 degrees C was maximal at 90 min, was saturable and partially reversible. Displacement studies with natural porcine motilin, synthetic leucine-motilin or norleucine-motilin indicated a dissociation constant (Kd) of 1.1 +/- 0.3 nM and a maximal binding capacity (Bmax) of 42 +/- 10 fmol/mg protein. Binding was unaffected by glucagon, pancreatic polypeptide and somatostatin, but substance P interfered via an unknown mechanism. By density gradient centrifugation motilin receptors were shown to be present in plasma membranes. Binding could only be demonstrated in preparations from antrum and upper duodenum. These observations provide evidence for a localized target region for motilin in the gastrointestinal tract, and for a direct interaction of motilin with gastrointestinal smooth muscle tissue.

Animals↗
PubMed1986

Comparison of the biological activity of canine and porcine motilin in rabbit.

The biological activity of porcine and canine motilin was studied in rabbits by establishing dose-response curves of both peptides using two different methods. The dissociation constant, obtained from the displacement of iodinated porcine motilin by canine motilin was 0.6 +/- 0.3 nM, versus 1.2 +/- 0.4 nM for porcine motilin. For the 13-norleucine and 13-leucine analogues of porcine motilin a value of 0.8 +/- 0.3 nM was obtained. Both motilins were almost equipotent in stimulating the in vitro contractile response of longitudinal smooth muscle strips: half-maximal effect was achieved at a concentration of 1.0 +/- 0.1 nM for canine versus 1.3 +/- 0.2 nM for the 13-norleucine analogue of porcine motilin. We conclude that porcine and canine motilin have a comparable bioactivity in the rabbit, although canine motilin is slightly more effective. The motilin receptor is probably specific for the N-terminal portion which is identical in both molecules.

Acetylcholine↗
PubMed1986

Somatostatin induces ectopic activity fronts via a local intestinal mechanism during fed state or pentagastrin.

The effect of local intra-arterial infusions of somatostatin on small bowel motility in the postprandial period and during an intravenous pentagastrin infusion was studied in five dogs. A Silastic catheter was implanted in a small branch of the superior mesenteric artery perfusing a 5-to 10-cm jejunal segment located 30-40 cm distally to Treitz. Small bowel myoelectric activity was recorded by means of a series of bipolar electrodes implanted subserosally along the small intestine. Experiments were started 2 wk after surgery and were performed in conscious animals. Intra-arterial infusion of somatostatin induced activity fronts in the fed state and during intravenous pentagastrin infusion in a dose-dependent manner. These activity fronts always started at or just below the perfused segment, migrated distally over the remaining small bowel, and were superimposed on the fed pattern. We conclude that local administration of somatostatin is able to initiate normally migrating ectopic activity fronts, despite the presence of neural and hormonal factors that control the fed state. Local release of somatostatin might be involved in the initiation of spontaneously occurring activity fronts.

Animals↗
PubMed1984

Different meals produce different digestive motility patterns.

The purpose of these experiments was to characterize the pattern of digestive myoelectric activity produced by four different test meals in dogs. A new approach for the analysis of the myoelectric activity of the small intestine was used. In contrast with methods dividing the tracings into present time periods, the present method respected the "motor entities," hence the continuity, of the tracing. Two types of motor entities occurred: "activity units" which are groups of consecutive slow waves with spiking, and "rest units," which are groups of consecutive slow waves without spiking. The frequency of occurrence and frequency of alternation of the various activity and rest units occurring during digestion was calculated. Digestive myoelectrical activity was characterized by the frequent occurrence and alternation of short activity and rest units. Three different patterns of digestive activity could be discriminated, ie, a fat, a protein and carbohydrate, and a canned food pattern.

Animals↗
PubMed1984

Somatostatin induces ectopic activity fronts of the migrating motor complex via a local intestinal mechanism.

To study the peripheral effect of somatostatin in dogs a tiny Silastic catheter was implanted in an almost terminal branch of the mesenteric artery, providing blood supply to a jejunal segment of 5-10 cm. In 4 dogs one catheter was implanted, perfusing a small bowel segment about 60 cm below the angle of Treitz; in 3 dogs two catheters were implanted, perfusing two small bowel segments about 30 and 60 cm below the angle of Treitz. The catheter was kept open by continuous perfusion with a diluted heparin solution by means of a portable insulin infusion pump fixed to the animal's protection jacket. Small bowel motility was recorded electromyographically. Experiments were started 2 wk after surgery and were performed in conscious fasted animals. Control experiments using intraarterial saline perfusion showed normal migrating motor complexes in the perfused segment. Intraarterial perfusion of somatostatin (50-200 ng/kg X h) induced ectopic activity fronts, which always started just distal to the perfused segment and progressed down the small bowel at a normal propagation velocity. During the occurrence of ectopic fronts no activity fronts were observed in the small bowel proximal to the perfusion site. Apart from ectopic fronts, normal activity fronts, starting in the duodenum and passing the perfused segment, were also observed. The most proximal part of the jejunum was more sensitive to intraarterial somatostatin than the more distal jejunum. Intravenous infusion of the same doses of somatostatin had no effect. Somatostatin, therefore, seems to induce ectopic fronts via a local mechanism. We propose that somatostatin is able to relieve the intestine locally from an inhibitory mechanism that prevents the development of activity fronts.

Action Potentials↗
PubMed1983

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.

Adult↗