Biomedical subjects

T L Peeters

Publications and source records attributed to T L Peeters.

At least 19 recordsLinked to original sources

PubMed2003

Differential effects of motilin on interdigestive motility of the human gastric antrum, pylorus, small intestine and gallbladder.

Motilin was infused in this study with the aim of examining refractory characteristics for motilin stimulation of antral phase III and fasting gallbladder emptying. Moreover, interdigestive pyloric and small intestinal motility from duodenum to ileum were studied, as these may be target organs for motilin. Eight fasting, healthy male volunteers received, on separate subsequent days, repeated infusions of 13leucine-motilin (8 pmol (kg min)(-1) for 5 min) or saline at 30 min after phase IIIs in the duodenum. Interdigestive motility of the antrum, pylorus, duodenum, jejunum and ileum was measured for maximum 10 h by using a 21-lumen perfused catheter. Gallbladder motility was measured by ultrasonography. Motilin infusions induced antral phase IIIs, but only after a preceding phase III of duodenal origin. Under this condition, time-interval to phase III at the duodenal recording site was 30 +/- 13 (SEM) min after motilin, compared with 79 +/- 14 min after saline (P < 0.01), and compared with 121 +/- 13 min for motilin infusion following an antral phase III (P < 0.001). Motilin did not affect small intestinal motility or isolated pyloric pressure waves (IPPWs). However, the number of IPPWs was significantly affected by the origin of the preceding phase III, irrespective of whether motilin or saline was infused. Gallbladder volume decreased significantly within 10 min after each motilin infusion. We conclude that this study clearly demonstrates differential regional effects of motilin. Motilin initiates antral phase IIIs, but stimulation is subject to a refractory period which is clearly prolonged after a preceding antral phase III. Motilin induced gallbladder emptying, however, is not subject to a refractory state. Small intestinal phase IIIs as well as pyloric IPPWs are not affected by motilin.

Adult↗

PubMed2003

Effects of Schistosoma mansoni infection on somatostatin and somatostatin receptor 2A expression in mouse ileum.

Intestinal schistosomiasis is accompanied by motility-related dysfunctions but the underlying mechanisms are not well-known. Therefore, the presence and effects on intestinal contractility of somatostatin (SOM) and its receptor, SSTR2A, were investigated in the ileum of normal and infected mice. The distribution of SOM and SSTR2A was visualized using immunocytochemistry. Radioimmunoassay combined with oogram studies was performed to determine SOM levels and contractility measurements were determined in organ bath experiments. Schistosomiasis resulted in a significant decrease in somatostatin-positive endocrine cells, whereas the number of somatostatin-immunoreactive (IR) neuronal cell bodies did not change. From 8 weeks postinfection onwards, an increase was noted in somatostatin-IR nerve fibres in both villi and granulomas. The staining intensity for SSTR2A, expressed in somatostatin-negative myenteric cholinergic neurones, increased during infection suggesting an upregulation of this receptor. SOM levels were negatively correlated with the number of eggs during the acute phase, and were elevated during the chronic phase. Pharmacological experiments revealed that schistosomiasis diminished the inhibitory effect of SOM on neurogenic contractions. We can conclude that schistosomiasis influences the distribution and expression levels of SOM and SSTR2A in the murine ileum, which might explain the changed motility pattern.

Adrenergic Fibers↗

PubMed2002

Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors.

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0-33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one-third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.

Adult↗

PubMed2001

Demonstration of a functional motilin receptor in TE671 cells from human cerebellum.

BACKGROUND: Our laboratory has described the presence of motilin receptors in the rabbit cerebellum. We discovered its presence in the human TE671 cell line, which is of cerebellar origin. METHODS: Cytosolic Ca(2+) fluxes were monitored on a confocal microscope in cells loaded with Indo-1 and stimulated with motilin under various conditions. Binding studies were performed with 125I-[Nle(13)]porcine motilin. Using primers, PCR for the motilin receptor was performed. RESULTS: Cells responded to motilin after 45+/-20 s. At different concentrations of motilin (10(-8), 10(-7), 10(-6.5), 10(-6) and 10(-5) M) the percentage of responding cells was 0+/-0, 0.6+/-1.5, 4.9+/-4.7, 21.7+/-15 and 35.7+/-12, respectively. The response was blocked by the motilin antagonists [Phe(3), Nle(13)]po-motilin (0.8+/-1.8%) and GM-109 (0.0+/-0.0%) and mimicked by the agonist ABT-229 (23.6+/-15%). After stimulation with motilin, ABT-229 or [Phe(3),Leu(13)]po-motilin, but not with the antagonist GM-109, cells were desensitized. The response to motilin persisted in Ca(2+)-free solution (22.8+/-14.7%), was not affected by nifedipine (44+/-11%) but was abolished by incubation with thapsigargin (0+/-0%). Neither ryanodine, nor a previous stimulation with caffeine (0+/-0%) in Ca(2+)-free Krebs, nor both could block the response to motilin (28, 32.0+/-5.7, 41.3+/-6.1%, respectively). Binding studies revealed two binding sites for motilin, with a pK(d) of 8.9+/-0.05 and 6.11+/-0.61 (n=4). There were 100 times more low than high affinity receptors per cell. The presence of receptor mRNA was confirmed by PCR. CONCLUSION: Functional motilin receptors are present in TE671 cells. The response requires intracellular IP(3)-sensitive Ca(2+) stores. These cells may serve as a model of the central motilin receptor.

Calcium Signaling↗

PubMed2001

Effect of recombinant human interleukin-11 on motilin and substance P release in normal and inflamed rabbits.

Recombinant human interleukin-11 (rhIL-11) normalizes depressed smooth muscle tension generation towards motilin and substance P (SP) in rabbits with colitis. The aim of this paper was to evaluate the effect of rhIL-11 treatment on motilin and SP release which could have an effect on the contractility changes. Rabbits received 4, 40, 72 or 720 microg/kg rhIL-11 s.c. or saline, 1 h later a continuous s.c. administration of rhIL-11 was started with or without the induction of colitis (135 mg/kg TNBS) for 5 days. Motilin and SP levels were measured by RIA, motilin mRNA expression by RT-PCR. TNBS-colitis did not affect plasma motilin levels but increased the motilin content of the duodenal mucosa 1.7-fold. rhIL-11 treatment dose-dependently increased plasma motilin levels (720 microg/kg day: 3.5-fold) and the motilin content of the duodenal mucosa (720 microg/kg day: 3.0-fold). The effects of rhIL-11 were similar in normal rabbits and were accompanied by an increased motilin mRNA expression. TNBS-colitis decreased plasma SP levels 2.7-fold and the SP content in the colonic muscle layer 7.1-fold. The decrease in the muscle layer, but not in the plasma, was normalized by rhIL-11 treatment. In normal rabbits, rhIL-11 caused a decrease in plasma SP levels, but had no effect on the tissue content of SP. In conclusion, treatment of inflamed or normal rabbits with rhIL-11 increases plasma and tissue levels of motilin in the duodenal mucosa via an increased expression of motilin in the endocrine cells and induces the release of SP from extrinsic neurons. These changes do not explain the beneficial effect of rhIL-11 on the lowered contractility in inflamed rabbits although a change in balance of neuropeptides may influence gastro-intestinal inflammation.

Animals↗

PubMed2001

Identification and expression of the motilin precursor in the guinea pig.

Motilin has never been isolated from rodents, the most frequently used laboratory animals, despite several attempts. We have isolated and sequenced the motilin precursor from duodenal mucosa of guinea pig (GenBank accession number AF323752) and studied its expression in several tissues. The percent homology with human motilin is the lowest yet observed due to several unique substitutions in the C-terminal end. As expected, the precursor was present in the gut mucosa with the exception of the gastric corpus. It was also present in medulla oblongata, nucleus of the solitary tract, hypophysis, spinal cord, hypothalamus, and cerebellum but not in the cerebral cortex. For the first time we demonstrated motilin expression in the thyroid.

Amino Acid Sequence↗

PubMed2001

Interdigestive gallbladder emptying, antroduodenal motility, and motilin release patterns are altered in cholesterol gallstone patients.

The role of interdigestive gallbladder emptying in gallstone formation is unknown. In fasting healthy subjects, gallbladder emptying is associated with antral phase III of the migrating motor complex (MMC) and high plasma motilin. Therefore, gallbladder volumes and motilin levels were measured during 13 MMC cycles in 10 cholesterol gallstone patients and compared with 20 MMC cycles in 10 healthy subjects. MMC cycle length was longer in gallstone patients than in healthy subjects (158.2 +/- 17.0 vs 105.5 +/- 10.4 min, respectively; P < 0.05), due to longer phase I (39.8 +/- 5.7 vs 17.2 +/- 3.7 min, respectively; P < 0.05). In contrast to healthy subjects, gallstone patients had no significant fluctuations of gallbladder volume during the MMC cycle, and motilin concentrations were not different in MMC cycles with phase III originating in antrum or duodenum. During MMC cycles with phase III originating in the duodenum, motilin levels were twice as high in gallstone patients as in healthy subjects (P < 0.002). In conclusion, cholesterol gallstone patients have an abnormal MMC and motilin release pattern. Their interdigestive gallbladder emptying is reduced and dissociated from the MMC. These disturbances may contribute to gallstone formation.

Cholelithiasis↗

PubMed2001

Contractile effects and intracellular Ca2+ signalling induced by motilin and erythromycin in the circular smooth muscle of human colon.

Motilin has excitatory effects on the colon of the rabbit and the dog, but little is known of its effect on the human colon. The aim of this study was to investigate the effects induced by motilin and erythromycin A (EMA) on muscle strips and on single cells from primary cultures from human colon. Isotonic contraction was recorded in circular muscle strips from macroscopically normal resection specimens of patients operated on for colonic neoplasm. Agonist-induced intracellular Ca2+ ([Ca2+]i) signalling was studied in primary cultures of colonic smooth-muscle cells using the ratiometric Ca2+ indicator Indo 1, on a laser-scanning confocal epifluorescence microscope. In circular muscle strips, norleucine13-porcine motilin ([Nle13]-pm)and EMA induced tonic contractions with an EC50 of 92 +/- 21 nmol L(-1) and 31 +/- 16 micromol L(-1), respectively. The maximal contraction was 21 +/- 4% (motilin) and 33 +/- 12% (EMA) of the response to 10(-4) mol L(-1) acetylcholine (ACh). The motilin antagonist OHM-11526 (10(-5.5) mol L(-1)) abolished the effects of both [Nle13]-pm and EMA. Neither tetrodotoxin (10(-5.5) mol L(-1)), L-nitro-D-arginine methyl ester (L-NAME) (10(-3.5) mol L(-1)) nor guanethidine (10(-5) mol L(-1)) interfered with the effects of [Nle13]-pm or EMA. [Nle13]-pm (10(-11)-10(-6) mol L(-1)) induced rises of [Ca2+]i in cultured colonic myocytes. At 10(-6) mol L-1, 94% of the cells responded, and half of the cells responded at 1.4 nmol L(-1) [Nle13]-pm. 81% (35/43) and 95% (75/79) responded to EMA (10(-6) mol L(-1)) and acetylcholine (ACh, 10(-4) mol L(-1)), respectively. The motilin antagonist GM-109 inhibited motilin- and EMA-induced [Ca2+]i rises. In the absence of extracellular Ca2+, only 13% (7/52) of the cells responded to [Nle13]-pm (10(-6) mol L(-1)) vs. 90% (47/52) to ACh (10(-4) mol L(-1)). Motilin and EMA have direct excitatory effects on circular smooth muscle from the human colon and these effects are mediated via a smooth-muscle motilin receptor. These findings suggest that motilin may regulate colonic motility and that motilides may have therapeutic potential for the treatment of colonic hypomotility.

Acetylcholine↗

PubMed2001

Motilin receptor density in inflamed and noninflamed tissue in rabbit TNBS-induced colitis.

Trinitrobenzenesulphonic acid (TNBS)-induced colitis decreases the contractile response of the rabbit colon to motilin, and inflammation may increase plasma motilin levels. We studied whether the decreased contractility could be due to a down-regulation of motilin receptors, caused by increased plasma motilin levels. As this would affect all tissues, uninflamed sites were studied as well. Colitis was induced by different doses (100-150 mg kg-1) of TNBS. In the colon, the TNBS dose-dependent decrease of the contractile response towards motilin was reflected in a decrease in motilin receptor density. In contrast, in the antrum, receptors were upregulated by 150 mg kg-1 TNBS, while central motilin receptors in the cerebellum were not affected. Plasma motilin levels were not influenced by inflammation, although the motilin content and mRNA expression in the duodenal and jejunal mucosa, but not in the colon, was significantly increased. The opposite was true for interleukin-1beta and interleukin receptor antagonist mRNA expression. We conclude that the decreased motilin contractility in rabbit colitis is due to a downregulation of motilin receptors in the colon, but this is not caused by chronic hormonal stimulation.

Animals↗

PubMed2001

Effects of intraduodenal bile on interdigestive gastrointestinal and gallbladder motility in healthy subjects.

BACKGROUND/AIMS: The enterohepatic circulation of bile acids is related to normal inter-digestive gastrointestinal motility, with the gut peptide motilin also being involved. This study aimed to investigate the effect of intraduodenal artificial bile infusion on antroduodenal and gallbladder motility so as to further elucidate the controlling factors. METHODS: Twelve fasting, healthy male volunteers received artificial bile (80 mol% bile acids; 15 mol% phospholipids; 5 mol% cholesterol) or placebo (saline) intraduodenally for 10 min starting 30 min after the end of phase III, according to a double-blind, randomised, cross-over design. Antroduodenal motility, gallbladder volumes, and plasma motilin levels were measured. All values are means +/- SEM. RESULTS: The interval between infusion and the subsequent phase III, as well as the origin of this phase III were not significantly different between bile and saline. Antral pressure waves were significantly more frequent during and immediately after bile infusion compared with saline infusion (p < 0.05). The duration of phase I following infusion was significantly longer after bile (24.8 +/- 3.7 min) than after saline infusion (13.1 +/- 1.7 min; p < 0.05). The mean gallbladder volume tended to increase in the hours following bile infusion, but to decrease after saline infusion (p = 0.06). Plasma motilin increased after bile and saline infusion in an almost identical way. CONCLUSION: This study provides no clear evidence for a role of intraduodenal artificial bile (i.e. its main constituents) in the regulation of migrating motor complex cycling or feedback inhibition of inter-digestive gallbladder emptying.

Adult↗

PubMed2001

GM-611 (Chugai Pharmaceutical).

GM-611 is an erythromycin derivative that acts as an agonist at the motilin receptor. It is being developed by Chugai as a potential treatment for gastric motility disorder [169036], as well as reflux esophagitis, non-ulcer dyspepsia and diabetic gastroparesis [347963]. GM-611 is in phase II trials in the US for reflux esophagitis [322624], [347955], [399349]. GM-611 acts by a novel mechanism whereby it stimulates and promotes peristalsis in the stomach and other segments of the gastrointestinal tract [334994]. The drug was shown to produce a dose-dependent sustained depolarization of rabbit duodenal smooth muscle. Depolarization appeared to be associated with activation of monovalent cation-selective channels [273336]. In December 2000, Credit Suisse First Boston predicted that successful development of GM-611 could lead to sales over $500 million [400228].

Animals↗

PubMed2000

Acute intraduodenal bile salt depletion leads to strong gallbladder contraction, altered antroduodenal motility and high plasma motilin levels in humans.

Cholecystokinin is the main hormone involved in postprandial gallbladder contraction. There is also considerable gallbladder contraction in the fasting state, associated with phase III of the gastrointestinal migrating motor complex and release of the hormone motilin. It has been proposed that intraduodenal bile salts exert a negative-feedback control on postprandial cholecystokinin release and resulting gallbladder contraction. We wanted to elucidate whether a similar control mechanism on gallbladder contraction exists in the fasting state. We therefore performed gallbladder ultrasonography and 24-h antroduodenal motility registrations and determined plasma cholecystokinin and motilin levels in six healthy subjects before and after acute (4 g) and chronic (8 days; 8 g day(-1)) oral cholestyramine. Acute cholestyramine strongly decreased gallbladder volumes and increased motilin without changed cholecystokinin levels. There was a negative relationship between gallbladder volumes and plasma motilin levels. Although there was a persistent fasting pattern of antroduodenal motility, its cycle length was increased (P < 0.03) with markedly longer phase II (P < 0. 005). Fasting gallbladder volumes 24 h later were still strongly decreased but gradually increased to pretreatment levels. Before and after 8 days cholestyramine, interdigestive and postprandial gallbladder emptying, intestinal migrating motor complex and hormone levels did not differ. We conclude that acute (but not chronic) intraduodenal bile salt depletion with cholestyramine affects gallbladder and antroduodenal motility, possibly partly related to motilin release.

Adult↗

PubMed2000

Dose-dependent effects of recombinant human interleukin-11 on contractile properties in rabbit 2,4,6-trinitrobenzene sulfonic acid colitis.

We studied the effect of recombinant human interleukin-11 (rhIL-11), a cytokine with protective effects against injury to the intestinal mucosa, on inflammatory changes in the muscle layers of the gut, in rabbits with colitis. A single dose of rhIL-11 (4, 40, or 720 microg/kg) was given 1 h before colitis was induced with 135 mg/kg 2, 4,6-trinitrobenzene sulfonic acid (TNBS), followed by a continuous s. c. administration of 4, 40, or 720 microg/kg. day rhIL-11 or saline for 5 days. Colitis affected mucosal architecture, general mechanical properties (passive tension increased with 12.3 g/mm(2), optimal stretch decreased with 26%), and collagen content (decreased from 366 +/- 25 to 237 +/- 13 microg/mg of protein). Changes in passive tension and collagen content were normalized by the highest and lowest dose of rhIL-11, respectively, but neither dose could normalize the optimal stretch. Colitis also decreased maximal contractile tension in response to acetylcholine (ACh), motilin, substance P (SP), K(+), and prostaglandin E(2) but this was normalized with 40 microg/kg. day (motilin, SP) and 720 microg/kg. day (ACh, K(+)) rhIL-11 but not for prostaglandin E(2). For motilin and SP, receptor density was decreased in colitis and normalized in treated rabbits. Colitis also increased the contractile potency toward ACh, an effect already reversed by rhIL-11, 4 microg/kg. day. In conclusion, rhIL-11 partially normalizes disturbed tension generation in experimental colitis. The use of this cytokine in the treatment of irritable bowel disease may contribute to the restoration of motor dysfunction.

Acetylcholine↗

PubMed2000

[Effect of central administration of motilin on the activity of gastric-related neurons in brain stem and gastric motility of rats].

To investigate the effect of microinjection of motilin into ventral medail hypothalamus (VMH) or intracerebroventricle (icv) on gastric motility, extracellular unit responses of dorsal vagal complex (DVC) in anesthetized rats and gastric motility of conscious rats were recorded. The results are as follows. (1) The firing rate of gastric distention related neurons in DVC was modified. (2) VMH and icv administration of motilin induced obvious enhancement in gastric motility. (3) The effect of motilin on gastric motility was abolished by vagotomy. These results imply that central motilin appears to work as an excitatory neuromodulator in the regulation of gastric motility through VMH-DVC-vagal nerve axis.

Animals↗

PubMed1999

Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats.

BACKGROUND/AIM: The effects of different prokinetic agents, the motilide erythromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were compared with that of granisetron, a 5-hydroxytryptamine (5-HT(3)) receptor antagonist, and a novel enterokinetic agent, prucalopride, a 5-HT(4) receptor agonist. METHODS: Different degrees of inhibition of gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy, or laparotomy plus mechanical stimulation of the gut. RESULTS: Metoclopramide decreased the transit after laparotomy with or without mechanical stimulation, whereas cisapride increased it after all three operations. Granisetron had no effect on the transit after the three operations when given alone. Prucalopride tended to increase the transit after laparotomy with or without mechanical stimulation when given alone. However, statistical significance was only reached when prucalopride was combined with granisetron. Erythromycin, a motilin receptor agonist, did not improve postoperative ileus in the rat. CONCLUSIONS: Cisapride, but not metoclopramide or erythromycin, is able to improve postoperative ileus in the rat. The results suggest that a combination of 5-HT(3) receptor antagonist and 5-HT(4) receptor agonist properties may be required to obtain a beneficial effect on surgery induced ileus in the rat. Furthermore, they indirectly indicate that stimulation of the excitatory mechanisms is not able to overcome the inhibitory influence of the neural reflex pathways activated during abdominal surgery.

Animals↗

PubMed1999

Region-specific antiproliferative effect of VIP and PACAP-(1-38) on rabbit enteric smooth muscle.

The ability of neuropeptides to modulate enteric smooth muscle proliferation was examined in primary explant cultures of rabbit gastric antrum and colon smooth muscle. Cell proliferation was determined by [3H]thymidine incorporation measurements and cell counting. Subcultured rabbit antrum and colon myocytes (passages 2-6) preserved a smooth muscle phenotype, as verified by immunohistochemistry for alpha-smooth muscle actin and electron microscopy. Both vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide-(1-38) [PACAP-(1-38)] concentration dependently (10(-10) to 10(-6) M) inhibited the serum-induced [3H]thymidine incorporation [in colon, 48.2 +/- 5.8 and 55.6 +/- 9.3% of control with 10(-6) M VIP and 10(-7) M PACAP-(1-38)] and inhibited increase in cell numbers in cultures derived from the colon but not in those from the antrum. Effects of VIP and PACAP-(1-38) were mimicked by forskolin (10(-7) to 10(-6) M) but not by 8-bromo-cGMP, whereas theophylline enhanced the effects of VIP. Inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester (10(-3.5) M) did not alter the effects of VIP. Substance P, motilin, calcitonin gene-related peptide, and somatostatin had no effect. A single class of 125I-labeled VIP binding sites was found in antrum and colon myocyte cultures with an equal affinity for VIP and PACAP-(1-38) [dissociation constant (Kd) in antrum = 3.4 +/- 0.8 nM for VIP and 2.0 +/- 1.0 nM for PACAP-(1-38); Kd in colon = 2.0 +/- 1.0 nM for VIP and 2.8 +/- 1.6 nM for PACAP-(1-38)]. Density of binding sites in the antrum was higher than in the colon. In disease states such as inflammatory bowel disease, inhibition of myocyte proliferation by VIP and PACAP may serve to control smooth muscle hyperplasia in the colon but not in the antrum.

Animals↗

PubMed1999

Differential changes in ACh-, motilin-, substance P-, and K(+)-induced contractility in rabbit colitis.

To test the hypothesis that the changes in intestinal contractility, which accompany inflammation of the gut, are agonist specific, we compared the response of inflamed strips to substance P (SP), motilin, ACh, and K(+) as a function of time. In parallel experiments, changes in the general mechanical properties (passive tension, optimal stretch) of the colitic tissue were evaluated. Colitis was induced by trinitrobenzenesulfonic acid, and rabbits were killed after 1, 2, 3, 5, or 8 days. Passive tension was increased starting from day 2 until day 8, and maximal active tension (T(max)) was generated at less stretch from day 5. A 50% decrease in T(max) was observed for ACh and K(+) between days 2 and 3 and for motilin and SP between days 3 and 5. For all compounds, T(max) returned to normal after 8 days. The pEC(50) value (negative logarithm of the concentration that induces 50% of the maximal contractile activity) for ACh was increased from day 3 until day 8 and for SP at day 3, whereas for motilin it was decreased at day 1. The changes in passive tension and optimal stretch indicate generalized structural alterations of smooth muscle tissue. However, the different time profiles of the changes in active tension and contractile potency for different contractile agents suggest that inflammation specifically affects receptor-mediated mechanisms.

Acetylcholine↗

PubMed1998

Localization of motilin binding sites in subcellular fractions from rabbit antral and colonic smooth muscle tissue.

BACKGROUND AND AIM: Motilin stimulates gastrointestinal motility, but in vitro studies reveal a direct smooth muscle effect, whereas in vivo studies reveal a neurally mediated effect. The aim of the present study was to determine if motilin binds to microsomes (smooth muscle) and/or synaptosomes (neurons). METHODS: Subcellular fractions were prepared from tissue of rabbit gastric antrum and colon by differential centrifugation and density gradient centrifugation and characterized by determining motilin binding and the presence of membrane markers. RESULTS: The purified microsomal fraction, enriched in the smooth muscle marker 5'-nucleotidase, was found to have the highest specific motilin binding in both antrum and colon. In the antrum, but not in the colon, the mitochondrial fraction also showed enrichment of [3H]-saxitoxin binding (marker for synaptosomes) and motilin binding, although the latter was much lower than in the microsomal fraction. Two receptor binding sites were characterized in both the antral mitochondrial/synaptosomal and colonic microsomal fraction (antrum: pKd,1 9.89+/-0.19, pKd,2 8.18+/-0.11, colon: pKd,1 9.72+/-0.31, pKd,2 8.39+/-0.58). CONCLUSION: Motilin binding is predominantly associated with smooth muscle membranes in both antrum and colon of the rabbit. In both organs two motilin binding sites are present with comparable affinities, but the density in the colon is much higher for both sites. Whether they represent neural and smooth muscle receptors will require studies with isolated smooth muscle cells and neurons.

Animals↗