Effect Of Motilin Research Articles

Effects of Motilin Receptor Agonists and Ghrelin in Human motilin receptor Transgenic Mice.

Gastrointestinal motility is regulated by neural factors and humoral factors. Both motilin and ghrelin improve gastrointestinal motility, but many issues remain unclear. We prepared human motilin receptor transgenic (Tg) mice and performed experiments evaluating the effects of motilin, erythromycin (EM), and ghrelin. EM and ghrelin promoted gastric emptying (GE) when administered either peripherally or centrally to Tg mice. Atropine (a muscarinic receptor antagonist) counteracted GE induced by centrally administered EM, but not that induced by peripherally administered EM. The administration of EM in this model promoted the effect of mosapride (a selective serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist), and improved loperamide (a μ-opioid receptor agonist)-induced gastroparesis. The level of acyl-ghrelin was significantly attenuated by EM administration. Thus, we have established an animal model appropriate for the evaluation of motilin receptor agonists. These data and the model are expected to facilitate the identification of novel compounds with clinical potential for relieving symptoms of dyspepsia and gastroparesis.

GABAergic and glutamatergic neurons in the brain regulate phase II of migrating motor contractions in the Suncus murinus.

Gastric contractions exhibit characteristic motor patterns in the fasted state, known as migrating motor contractions (MMC). MMC consist of three periodically repeated phases (phase I, II and III) and are known to be regulated by hormones and the autonomic and enteric nervous systems. However, the central regulation of gastric contractions in the fasted state is not completely understood. Here, we have examined the central effects of motilin, ghrelin, γ-aminobutyric acid (GABA) and L-glutamate signaling on gastric MMC by using suncus (Suncus murinus) as an animal model, because of their similar gastric motor patterns to those observed in humans and dogs. Intracerebroventricular (i.c.v.) administration of motilin and ghrelin had no effect on phase I and II contractions, respectively. Conversely, i.c.v. administration of GABAA receptor antagonist, during phase I of the MMC, evoked phase II-like contractions and significantly increased the motility index (MI). This was compared with the i.c.v. administration of GABA which inhibited spontaneous phase II contractions with a significantly decreased MI. In addition, i.c.v. administration of L-glutamate during phase I also induced phase II-like irregular contractions with a significant increase in the MI. Taken together with previous findings, these results suggest that central GABAergic and glutamatergic signaling, with the coordination of both peripheral motilin and ghrelin, regulate phase II contractions of MMC in the fasted state.

The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew

The migrating motor complex (MMC) is responsible for emptying the stomach during the interdigestive period, in preparation for the next meal. It is known that gastric phase III of MMC starts from the proximal stomach and propagates the contraction downwards. We hypothesized that a certain region of the stomach must be more responsive to motilin than others, and that motilin-induced strong gastric contractions propagate from that site. Stomachs of the Suncus or Asian house shrew, a small insectivorous mammal, were dissected and the fundus, proximal corpus, distal corpus, and antrum were examined to study the effect of motilin using an organ bath experiment. Motilin-induced contractions differed in different parts of the stomach. Only the proximal corpus induced gastric contraction even at motilin 10(-10) M, and strong contraction was induced by motilin 10(-9) M in all parts of the stomach. The GPR38 mRNA expression was also higher in the proximal corpus than in the other sections, and the lowest expression was observed in the antrum. GPR38 mRNA expression varied with low expression in the mucosal layer and high expression in the muscle layer. Additionally, motilin-induced contractions in each dissected part of the stomach were inhibited by tetrodotoxin and atropine pretreatment. These results suggest that motilin reactivity is not consistent throughout the stomach, and an area of the proximal corpus including the cardia is the most sensitive to motilin.

Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus

Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus.

Motilin stimulates pepsinogen secretion in Suncus murinus

Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in suncus.

Mechanism of motilin-mediated inhibition on voltage-dependent potassium currents in hippocampal neurons

ObjectiveThe effects of motilin on voltage-dependent K+ currents in hippocampal neurons with the addition of l-arginine (l-AA), d-arginine (d-AA) and N-nitro-l-arginine methyl ester (l-NAME) were investigated in this study. MethodsMice (1–3days old) were randomly assigned to different groups according to the addition of motilin, l-AA, d-AA, and l-NAME. The K+ current signals were detected by the whole-cell patch-clamp technique. ResultsCompared with the control group, the transient outward voltage-dependent K+ current was significantly inhibited by motilin added with l-AA. In contrast, the addition of motilin and l-NAME significantly increased the K+ current, while no significant change was detected by the addition of motilin accompanied with d-AA. ConclusionThe inhibiting effects of motilin on the voltage-dependent K+ current in hippocampal neurons indicate that motilin acts as a regulatory factor for the nitric oxide pathway.

Can small non‐peptide motilin agonists force a breakthrough as gastroprokinetic drugs?

GSK962040 is a small selective motilin receptor agonist currently under investigation in clinical trials for the treatment of conditions associated with delayed gastric emptying. As reported in this issue of the British Journal of Pharmacology, Broad et al., studied for the first time the region-dependent contractile effects of motilin and GSK962040 in human smooth muscle strips. Both compounds facilitated cholinergically mediated contractions of human gastric antral muscle strips at low concentrations and induced smooth muscle contractions at high concentrations. The effect was less pronounced in the fundus and almost absent in the colon. The long-lasting facilitation of cholinergic responses in the antrum by GSK962040 compared with the fading responses to motilin may be of importance from a clinical point of view. The approach used by Broad et al. with human tissue is a validated model to identify motilin receptor agonists with therapeutic value.

Effects of motilin on potassium and calcium currents of rat's proximal colon smooth muscle cells

Objective To investigate the effects of motilin on the voltage dependent potassium channel and L-type calcium channel currents in rat proximal colon smooth muscle cells (PCSM) and to explore its mechanism in increasing colonic motility.Methods PCSM were isolated by collagenase.The voltage dependent potassium channel transit outward current (IKA ) and delayed rectifier current (IKdr) and L-type calcium currents (ICa(L)) were measured by whole cell patch clamp technique.Groups were analyzed by paired t-test.Results There was no significant effect of motilin on IKA and IKdr.L-type calcium channel was dose-dependently activated by motilin from 0.5 × 105 mmol/L to 10.0 ×10-5 mmol/L.At 6 × 10-5 mmol/L motilin and under - 10,0 and 10 mV stimulating voltage,maximum current density increased by 154.61％,62.69％ and 21.02％ respectively and activation kinetics curve obviously left shifted.Half activation voltage decreased from (2.740±1.211) mV prior administration to ( - 25.290 ± 0.614) mV (t =8.534,P =0.007 ) and there was no significant difference in slope factor. Conclusions Motilin increases colonic smooth muscle contraction by promoting calcium influx. However the frequency of colonic smooth muscle contraction could not change with frequency of equilibrium potential and action potential of colonic smooth muscle. Key words: Motilin; Patch-clamp techniques; Potassium channels; Calcium channels, L-type; Muscle, smooth; Colon; Rats

Motilin beyond gut motility: a novel role in the regulation of adipose tissue metabolism

MOTILIN IS A 22 AMINO ACID PEPTIDE present predominantly in endocrine cells of the duodenal mucosa, although it can also be found in the myenteric plexus and the thyroid gland, as well as in the brain, with the highest concentration detected in the hypothalamus (3). The orphan G protein-coupled receptor (GPR38) has been identified as the human motilin receptor, which is mainly found in the gastrointestinal (GI) tract in a species-dependent manner (3). Motilin is well known for its GI motor-stimulating properties. Its plasma concentration increases cyclically every 90‐120 min during the interdigestive fasting period to generate short intervals of strong peristaltic contractions from the stomach toward the duodenum and the small intestine. This pattern of peristaltic contractions is known as the phase III contraction of the migrating motor complex (8, 10). Most of the research regarding the role of motilin has focused on understanding the mechanisms undelying the motor-stimulating (prokinetic) properties of this peptide in the GI tract. This was further propelled by the observations that motilin could accelerate gastric emptying in patients with diabetic gastroparesis with important therapeutic applications for this peptide (5, 9, 11). The major interest has been to develop motilin agonists for the treatment of hypomobility disorders of the GI tract. In this context, very little is currently known about potential effects of motilin beyond its role in the regulation of GI tract motility. The article in this issue by Miegueu et al. (7) provides novel and compelling evidence that

Motilin stimulates preadipocyte proliferation and differentiation and adipocyte lipid storage

Motilin is a circulating gastrointestinal peptide secreted primarily by duodenal mucosal M cells and recognized for its prokinetic effects on gastrointestinal tissues. Little information is available regarding effects on insulin/glucose homeostasis or adipocyte function. Our aim was to evaluate the effects of motilin on adipocyte proliferation, differentiation, lipolysis, and macronutrient uptake in adipocytes. 3T3-L1 cells and primary rat adipocytes were treated acutely and chronically with varying motilin concentrations, and effects were compared with vehicle alone (control), set as 100% for all assays. In preadipocytes, motilin stimulated proliferation ([(3)H]thymidine incorporation) and mitochondrial activity (141 ± 10%, P < 0.001 and 158 ± 10%, respectively, P < 0.001), in a concentration-dependent manner. Chronic supplementation with motilin during differentiation further increased lipogenesis (Oil red O staining 191 ± 27%, P < 0.05) and was associated with an upregulation of PPARγ (148 ± 8%, P < 0.01), C/EBPα (142 ± 17%, P < 0.05), and Cav3 (166 ± 20%, P < 0.05) expression. In mature 3T3-L1 adipocytes motilin increased fatty acid uptake/incorporation (≤ 202 ± 12%; P < 0.01) and glucose uptake (146 ± 9% P < 0.05) and decreased net fatty acid release (maximal -31%, P < 0.05) without influencing total lipolysis (glycerol release). Similar effects were obtained in primary rat adipocytes. Motilin acutely increased expression of PPARγ, CEBPβ, DGAT1, and CD36 while decreasing adiponectin mRNA and secretion. In human adipose tissue, motilin receptor GPR38 correlated with HOMA-IR and GHSR1 (r = 0.876, P < 0.0001). Motilin binding and fatty acid incorporation into adipocytes were inhibited by antagonists MB10 and [D-lys3]-GRP6 and PI 3-kinase inhibitor wortmannin. Taken together, these results suggest that motilin may directly influence adipocyte functions by stimulating energy storage.

Effect of motilin on gastric distension sensitive neurons in arcuate nucleus and gastric motility in rat

Intestinal motilin is known to stimulate gastrointestinal (GI) motility and the arcuate nucleus (Arc) of hypothalamus is shown to be involved in the regulation of GI motility. Single unit discharges in the Arc were recorded extracellularly by implantation of a force transducer into the stomach in rats, to evaluate the effect of motilin on gastric motility. Projection of nerve fiber and expression of motilin were observed by retrograde tracer deposits of Fluoro-Gold (FG) and fluo-immunohistochemistry staining. 65.5% of neurons in Arc responded to gastric distension (GD), 55.6% of which showed excitation (GD-E), and 44.4% showed inhibition (GD-I). After GD, the firing rate of GD-E neurons significantly increased (P<0.01), but decreased for GD-I neurons (P<0.01). Most of both GD-E and GD-I neurons were activated by motilin (P<0.05). The frequency and amplitude of gastric contractions significantly increased by administration of motilin in Arc with a dose dependent manner (P<0.05-0.01). However, pretreatment with GM109 could abolish the responses of neurons and excitatory effect of gastric motility induced by motilin. Motilin immunoreactive neurons were increased in Arc via gastric distention (P<0.05). Motilin/FG-labeled neurons were detected in hypothalamus paraventricular nucleus (PVN). Our findings suggest that motilin neurons in Arc may accept peripheral somatosensory afferent inputs from gastric mechanoreceptors of the stomach, and also may acts as a stimulatory factor in Arc to regulate gastric motility via some inferior nucleus relay pathway. The results provide insight into the role of Arc in the control of digestion mediated via motilin.

146 - Effect of motilin in preadipocyte proliferation and differentiation

Introduction: Motilin is a circulating gastrointestinal peptide and recognized for its prokinetic effects on gastrointestinal tissues. Little information is available regarding non-gastrointestinal functions, although effects on insulin-glucose homeostasis and food intake are suggested. The present study was designed to evaluate the effect of motilin on preadipocyte proliferation and differentiation, and macronutrient uptake in adipocytes.

Effect of thyroid motilin on migrating motor complex in fasting rats

Objective:To investigate the effects of thyroid motilin(MTL) on migrating motor complex(MMC) in fasting rats.Methods: The distribution and quantitative expression of motilin in the thyroids were detected by immunohistochemistry and radioimmunoassay.We also observed the effect of thyriod motilin on the MMC by recording the gastrointestinal motility in conscious rats.Results: Tail vein injection of MTL increased MMC in antrum and duodenum in a dose-dependent manner,as manifested by increased contraction frequency and amplitude(P0.05,P0.01).However,the contraction frequency and amplitude were significantly decreased after injection of MTL-R antagonist GM109(P0.05).GM109 could obviously block the promoting effect of MTL on MMC.Removing left thyroid significantly increased MMC cycle,contraction amplitude,and decreased contraction frequency(P0.05).Injection of anti-MTL serum into the thyroids could significantly promote MMC and increase the frequency and amplitude of contraction(P0.05).Immunohistochemistry demonstrated that motilin immunoreactive(MTL-IR) cells,together with calcitonin(CT),were observed in the thyroids,indicating the expression of MTL in thyroid C-cells.Radioimmunoassay analyses displayed that MTL level in the duodenal mucosa was 128.02 and 100.57 times those in the antrum and thyroid,respectively.Conclusion: MTL is expressed in the thyroid C-cell and participates in the regulation of MMC.

Effects of motilin on intracellular free calcium in cultured smooth muscle cells from the antrum of neonatal rats

The aim of this study was to determine the effects of motilin on [Ca(2+)](i) regulation and its underlying molecular mechanism in cultured antral smooth muscle cells (ASMCs). Antral cells were isolated and cultured from neonatal rats, and then the [Ca(2+)](i) in these cells was evaluated by calcium fluorescent probe Fluo-3/AM on a laser scanning confocal microscope. We show that motilin dose-dependently increased [Ca(2+)](i) concentration in cultured ASMCs. Pre-incubation of cells with either the calcium antagonist verapamil (10(-5) mol L(-1)) or the calcium chelator Egtazic (EGTA, 0.1 mmol L(-1)) significantly suppressed motilin (10(-6) mol L(-1)) induced [Ca(2+)](i) increase as indicated by fluorescent intensity. Interestingly, after mixing with the non-selective intracellular calcium release blocker TMB-8 (10(-5) mol L(-1)), guanosine triphosphate regulatory protein antagonist NEM (10(-5) mol L(-1)), phospholipase C (PLC) inhibitor compound 48/80 (1.2 microg mL(-1)) and ryanodine at high concentration (10(-5) mol L(-1)), the motilin-induced [Ca(2+)](i) increase was only partially blocked. The protein kinase C inhibitor d-sphingosine (10(-6) mol L(-1)), however, did not show any inhibitory effect on motilin-induced [Ca(2+)](i) elevation. Our study suggests that motilin-stimulated [Ca(2+)](i) elevation in ASMCs is probably due to sustained extracellular Ca(2+) influx and Ca(2+) release from Ca(2+) stores via inositol tris-phosphate receptors and ryanodine receptors. Specifically, motilin-induced [Ca(2+)](i) release is accompanied with guanosine triphosphate-binding protein-coupled receptor-PLC-inositol tris-phosphate signalling cascades.

Colitis affects the smooth muscle and neural response to motilin in the rabbit antrum

The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum. Myeloperoxidase (MPO) activity, NF-kappaB activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6-trinitrobenzenesulphonic acid colitis. Smooth muscle and neural responses to motilin were studied in antral smooth muscle strips in vitro. Colitis did not affect MPO activity, but increased NF-kappaB activity in the antrum. Motilin receptor density in the antrum was not affected. Under control conditions, motilin induced a slowly developing tonic smooth muscle contraction. Five days post-inflammation, tonic contractions to motilin were reduced and preceded by a rapid initial contraction. Other kinases were recruited for the phosphorylation of myosin light chain (MLC) (a multi-functional MLC kinase), and for the inhibition of MLC phosphatase (Rho kinase in addition to protein kinase C) to mediate the motilin-induced contractions during inflammation. Colitis potentiated the cholinergic neural on-contractions in the antrum. This was associated with a hyper-reactivity to motilin and an increased muscle response to ACh. Colitis altered the course of the motilin-induced smooth muscle contraction in the antrum. This involved changes in the kinases phosphorylating MLC. Increased cholinergic excitability to motilin in the antrum may play a role in the pathogenesis of inflammation-associated gastric motility disorders.

Effect of motilin on the contractility of gastric smooth muscle via NO pathway in guinea pigs

Abstract This study investigates the gastroprokinetic effects of motilin and erythromycin A (EM-A) and its potential mechanism in guinea pigs Cavia porcellus in vitro. Guinea pig stomach strips were mounted under organ baths containing Krebs solution. Motilin, EM-A, Nω-Nitro-L-arginine (L-NNA), L-arginine (L-AA) were added to the bathing solution in a non-cumulative way. Then the effects of motilin and EM-A was studied during electrical field stimulation (EFS) in the absence and presence of L-NNA and L-AA in the gastric anturm and fundus of guinea pigs. In addition, we observed the co-expression of motilin receptors and neuronal nitric oxide synthase (nNOS) in the gastric myenteric plexus of guinea pigs by fluo-immunohistochemistry. The results showed that the circular muscle tissues of the gastric fundus generated on-relaxations and off-contractions with the frequency of 1 - 16 Hz. The on-responses induced a relaxation' partially mediated by the release of nitric oxide (NO) because addition of L-NNA turned the relaxations into cholinergically mediated contractions. The off- contractions were also cholinergically mediated as they disappeared under non-adrenergic, non-cholinergic (NANC) conditions using atropine and guanethidine. In fundic strips, motilin and EM-A induced on-relaxation and off- contraction and both motilin (1 µmol/L) and EM-A (100 µmol/L) may significantly increased on- response and reduced off-response (P &lt; 0.05). And the effects of motilin on strip responses were significantly enhanced compared with EM-A. The on-responses could be reversed into a cholinergically mediated contraction by addition of NOS inhibitors L-NNA. In contrast, administration of substrate of NOS, L-AA, significantly increased on-relaxations and reduced cholinergic motor responses which were induced by motilin or EM-A. However D-arginine (D-AA) did not change the above response induced by motilin or EM-A. In the antral strips, motilin and EM-A only increased off-contractions. The response to motilin and EM-A in the presence of L-NNA did differ from that obtained with L-NNA alone. It showed that both motilin and EM-A could enhance off-contractions induced by L-NNA (P &lt; 0.05). Immunohistochemistry study showed that motilin receptor immunoreactive positive neurons were co-localized with nNOS positive neurons in the gastric myenteric plexus of the guinea pigs. These results suggested that motilin or EM-A modulates gastrointestinal motility which was mediated by activating gastric nervous and NO pathways in guinea pigs gastro-intestinal tract.

S1678 Comparison of Ghrelin and Motilin Effects On Fasted Gastric Tone and Gastric Accommodation to Meal in Conscious Dogs

S1678 Comparison of Ghrelin and Motilin Effects On Fasted Gastric Tone and Gastric Accommodation to Meal in Conscious Dogs

Effect of motilin on the discharge of rat hippocampal neurons responding to gastric distension and its potential mechanism

The study aims to find the effect of motilin on neuronal activity of gastric distension-responsive neurons in rat hippocampus and its possible mechanism. Single unit discharges in the hippocampal CA1 region were recorded extracellularly by means of four-barrel glass micropipettes in anesthetized rats and the expression of nNOS in hippocampus was observed by fluo-immunohistochemistry staining. Of the 171 recorded neurons, 76.0% were GD-excitatory (GD-E) neurons and 24.0% were GD-inhibited (GD-I) neurons. The 57.6% of GD-E neurons showed an excitatory response to motilin and the same effect was observed in 51.7% GD-I neurons. However, when NOS inhibitor nitro- l-arginine methyl ester ( l-NAME) was administrated previously, the followed motilin-induced excitatory responsiveness of GD-responsive neurons was reduced. In contrast, discharge activity of GD-responsive neurons with motilin was enhanced by pretreatment of NO precursor l-arginine. The expression of nNOS-IR positive neurons was significantly increased in CA1 after administration of motilin. Our findings suggested that motilin excited the GD-responsive neurons in the hippocampal CA1 region and the excitatory effect of motilin may be mediated by the endogenous NO.

Distribution and electrophysiological effects of motilin in Purkinje cells

Evidence exists that motilin immunoreactivity is highly expressed in Purkinje cells. In this study, immunohistochemistry and whole-cell patch-clamp recording were performed to investigate the spatial distribution and electrophysiological effects of motilin receptors in the cerebellum. We show here that motilin receptors are strongly expressed in Purkinje cells of the human and rat cerebellum. Motilin at 10 nM depolarized Purkinje cells of the rat cerebellum, and this was mimicked by the motilin receptor agonist erythromycin. The depolarization evoked by motilin persisted in the presence of tetrodotoxin, glutamate and gamma-amino-n-butyric acid receptor antagonists, indicating that motilin excited the Purkinje cells by activating the receptor expressed on the neurons recorded. We suggest that motilin may serve specific neural functions in the cerebellum.

Effects of Motilin and Mitemcinal (GM-611) on Gastrointestinal Contractile Activity in Rhesus Monkeys In Vivo and In Vitro

Neither the presence of motilin receptors nor their action has been investigated in monkeys. The object of this study was to determine the effects of motilin and mitemcinal (GM-611), an erythromycin derivative, on the gastrointestinal tract in rhesus monkeys in vivo and in vitro. In in vivo investigations in conscious monkeys, both motilin and mitemcinal induced migrating motor complex-like contractions in the interdigestive state and also accelerated gastric emptying. In in vitro investigations, the presence of motilin receptors in the gastrointestinal tract was demonstrated by receptor binding assays. Motilin and mitemcinal contracted isolated duodenum strips in a concentration-dependent manner. In conclusion, rhesus monkeys may be useful for studying the physiological and pharmacological roles of the motilin agonistic mechanism because they show reactivity to motilin both in vivo and in vitro.