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Keywords:

  • cisapride;
  • gastric emptying;
  • prokinetic agent;
  • smooth muscle motility;
  • Taraxacum officinale

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References

Background Taraxacum officinale (TO) is a traditional herbal medicine that has been widely used for abdominal illnesses. However, the efficacy and the mechanism of TO on gastric emptying (GE) and smooth muscle motility are unknown.

Methods  Ethyl acetate fraction (EA), n-butanol fraction (BF), and aqueous fraction (AF) were prepared in succession from 70% ethanol extract (EE) of TO using solvent polarity chromatography. Phenol red meal was adopted to estimate GE in mice. A polygraph was used to measure the smooth muscle motility in rats.

Key Results  The percentage of GE was 48.8 ± 6.1% (vehicle control), 75.3 ± 6.5% (cisapride positive control), 68.0 ± 6.7% (EE), 53.3 ± 6.0% (EA), 54.1 ± 6.3% (AF), and 86.0 ± 6.5% (BF). Thus, BF was determined to be most effective in accelerating GE. This stimulatory effect of BF on GE was also supported by the observation that BF increased spontaneous contraction of gastric fundus and antrum and decreased the spontaneous motility of pyloric sphincter in vitro. Atropine blocked the stimulatory effect of BF on GE, whereas phentolamine and propranolol had no effect.

Conclusions & Inferences  BF seems to be a promising prokinetic agent. BF-induced increase in the contraction of fundus and antrum contributes to an increase in the intra-gastric pressure. BF-induced decrease in the motility of pyloric sphincter contributes to a decrease in the resistance of food from the stomach to the small intestine. The acceleration of GE by BF is likely to be exerted through cholinergic stimulation.


Abbreviations:
TO

Taraxacum officinale

EE

ethanol extractant from Taraxacum officinale

GE

gastric emptying

EA

ethyl acetate fraction

BF

n-butanol fraction

AF

aqueous fraction

CSP

cisapride

ED50

median effective dose

ICC

interstitial cells of Cajal

ICC-MY

ICC in the myenteric plexus

ICC-IM

intramuscular ICC

DMSO

dimethylsulfoxide

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References

Disorders of stomach motility are involved in functional gastroenterological diseases such as gastro-esophageal reflux disease, functional dyspepsia,1 gastroparesis,2 and postoperative gastrointestinal atony.3 Prokinetic agents such as domperidone and cisapride (CSP) are important therapeutic drugs, 4,5 but these biochemically synthesized drugs have some side-effects such as prolongation of the QT interval and cardiac arrhythmias.6,7 Therefore, natural products are important for the prevention and treatment of gastrointestinal disorders.8Taraxacum officinale (TO), also called dandelion, is a traditional oriental medicine that has long been used for the treatment of abdominal distention, dyspepsia, nausea, and vomiting.9 It was also commonly used in Native American medicine to remedy stomach upset and heartburn.9Taraxacum officinale root and leaf are used widely in Europe for gastrointestinal ailments. The German Commission E and European Scientific Cooperative for Phytotherapy (ESCOP) recommend TO root to treat stomach upset, dyspepsia, and loss of appetite.10,11 In addition, it has been shown that TO produces notable contraction of colonic smooth muscle cells in rats.12 Overall, multiple lines of evidence suggest that TO may have some effects on gastrointestinal smooth muscle motility. However, the potential role of TO in gastric emptying (GE) and gastric smooth muscle motility is unknown. Therefore, the aim of this study was to examine the activity of TO and its fractions on GE. As GE has been shown to be related to smooth muscle contraction,13 we investigate the effect of the most effective fraction [n-butanol fraction (BF)], obtained from TO, on the motility of gastric fundus, antrum, and pyloric sphincter. In addition, some antagonists were used to track down possible sites of the BF-induced stimulatory effect on GE.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References

Preparation of TO extracts

Taraxacum officinale was collected in Changbai Mountain area of Jilin Province, China and authenticated by Prof. Hui-Shan Piao and Prof. Yong-Zhen Liu. A specimen (RJ 20000807-1) is deposited in the Herbarium of Yanbian University, College of Medicine, China. Dried whole plants of TO (3.8 kg) were cut into small pieces and percolated for 30 days with 70% ethanol at room temperature. The extract was then filtered (Whatmann paper no. 4) and concentrated in a rotary evaporator (Buchi; St. Gallen, Switzerland) in vacuo. Finally, the concentrated ethanol extractant (EE) was partitioned successively with equal volumes of ethyl acetate and n-butanol; each fraction was then evaporated in vacuo to yield the residues of ethyl acetate fraction (EA, 497.8 g, 13.1%), n-butanol fraction (BF, 634.6 g, 16.7%), and aqueous fraction (AF, 266.7 g, 70.2%).

Animals

Male Balb/c mice (18–22 g) and Wistar rats (200–260 g) were provided by the Experimental Animal Center of Yanbian University Medical College (Yanji, Jilin, China). All experiments were performed in accordance with the National Institutes of Health (NIH) guide for the Care and Use of Laboratory Animals. The experimental procedures were approved by the Ethical Committee for the Experimental Use of Animals at Yanbian University.

Gastric emptying

The standard method of phenol red marker meal was employed as described previously.14,15 Gastric emptying was determined with a modification of the reported procedure.16 Mice were allowed free access to water until 3 h before the subcutaneous administration of the test drugs (EE, EA, BF, AF, and CSP) in a volume of 0.2 mL at the concentration of 100 mg kg−1 bodyweight (bw). A solution of 0.1% (w/v) phenol red in aqueous sodium carboxymethylcellulose (1.5% w/v) was used as a test meal. Each test drug was given 1 h before the oral administration of the test meal. Twenty minutes after the administration of the test meal, the animal was sacrificed. The stomach was then exposed by laparotomy and removed. The animals treated with the vehicle (saline, 0.9% sodium chloride solution, 0.2 mL) were sacrificed immediately after the oral administration of the test meal and the phenol red content in the stomach was considered as the standard (100%). The removed stomach was incised in 40 mL of NaOH solution (0.1 N) and its content was dissolved. A 1-mL aliquot of the supernatant was added to 2 mL of trichloroacetic acid (7.5% w/v) to precipitate the proteins. After centrifugation (2500 g) for 20 min, 1 mL of the supernatant was added to 1 mL of NaOH (1 N) to develop the maximum intensity of the color. The absorbance at 558 nm of the solution was then measured with a spectrophotometer (U-1080; Hitachi Ltd., Tokyo, Japan). The gastric emptying for each mouse was calculated according to the following formula:

  • image

where X is the absorbance of phenol red remaining in the stomach 20 min after phenol red administration and Y is the mean absorbance of phenol red recovered from the stomachs of control mice immediately after phenol red administration.

Smooth muscle motility

The smooth muscle motility was assessed with a modification of the previous study.17 Male Wistar rats were anesthetized with ethyl carbamate (1 g kg−1). The abdomen of each animal was opened along the midline. The stomach was removed and placed in a pre-oxygenated Tyrode solution. The mucosal layer was then removed. The long axis of the stomach was cut parallel to the circular muscle fibers and strips of the circular muscle layer (2 × 10 mm) were prepared. The muscle strip was placed in a chamber (10 mL volume) containing Tyrode solution. The solution was constantly provided with oxygen and maintained at 37 ± 0.5°C by a thermostat (WC/09-05; Chongqing Experimental Instrument Co, Chongqing, China). One end of the strip was fixed to the floor of the chamber and the other end was attached to an isotonic transducer (TD112S; Nihon Kohden, Tokyo, Japan) to record motility of the muscle strip. The motility of the strips was recorded successively on the polygraphs (RM6200; Nihon Kohden).

After incubation of the muscle strips for approximately 30 min, spontaneous motility of the strips was observed. After a 50-min equilibration period, BF (0.01 mL) and CSP (0.01 mL) were added to the bath at a concentration of 50 and 2 mg L−1, respectively. The phasic and tonic contractions of the fundus, antrum, and pylorus were analyzed as the average strength of contraction over the number of contractions in the 3-min period before and after the administration of BF and CSP. When stable responses were observed, BF or CSP was washed out with Tyrode solution for four times with 5-min time intervals.

Experimental design

To determine the most effective fraction on GE, mice were allocated randomly to a control group (n = 8, 0.2 mL saline, s.c.), experimental groups (n = 8–9, 0.2 mL EE, EA, BF, and AF at the concentration of 100 mg kg−1 bw, s.c.), and a positive control CSP group (n = 8, 0.2 mL CSP at the concentration of 2 mg kg−1 bw, s.c.). The BF was determined to be most effective based on GE activity (Fig. 1).

image

Figure 1.  Effect of ethanol extract (EE), ethyl acetate fraction (EA), n-butanol fraction (BF), aqueous fraction (AF), and cisapride (CSP) on gastric emptying (GE). Ethanol extract produced an increase in GE. Among the fractions of EE, BF is most effective. Cisapride, a prokinetic agent, was used as a positive control. **P < 0.01 vs control (Con).

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To determine the optimal dosages, we investigated the effects of BF at different concentrations (0.1, 1, 10, 20, 50, and 100 mg kg−1 bw, 0.2 mL s.c.) on GE in mice (n = 8 in each group, Fig. 2).

image

Figure 2.  Dose-dependent stimulation of gastric emptying (GE) by n-butanol fraction (BF). The dose–response curve shows that the median effective dose (ED50) was 20.1 mg kg−1.

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To investigate the effect of BF on gastric smooth muscle motility, we added BF to the bath solution at the concentration of 50 mg L−1. After stable responses were observed, the muscle strips were rinsed with Tyrode solution three to four times (5-min time interval). The solution of 0.01% DMSO did not affect smooth muscle motility (data not shown).

To trace down the possible sites of BF-induced stimulatory effect on GE, mice were allocated randomly to a control group (0.2 mL saline i.p. plus 0.2 mL saline s.c.), BF group (0.2 mL saline i.p. plus 0.2 mL BF s.c.), atropine group (0.2 mL atropine i.p. plus 0.2 mL saline s.c.), atropine plus BF group (0.2 mL atropine i.p. plus 0.2 mL BF s.c.), phentolamine group (0.2 mL phentolamine i.p. plus 0.2 mL saline s.c.), phentolamine plus BF group (0.2 mL phentolamine i.p. plus 0.2 mL BF s.c.), propranolol group (0.2 mL propranolol i.p plus 0.2 mL saline s.c.), and propranolol plus BF group (0.2 mL propranolol i.p. plus 0.2 mL BF s.c.). Saline or atropine or phentolamine (1.0 mg kg−1) or propranolol (1.0 mg kg−1) was injected intraperitoneally 15 min before the subcutaneous administration of saline or BF (100 mg kg−1).

Drugs and solution

The Tyrode solution used in this study contained (mmol L−1): NaCl 147, KCl 4, CaCl2 2, MgCl2 1.05, NaH2PO4 0.42, Na2HPO4 1.81 and glucose 5.5; pH was adjusted to 7.4 with NaOH and the solution was bubbled with oxygen. Cisapride was dissolved in dimethylsulfoxide (DMSO) to 20 mg mL−1 and then diluted with distilled water to make a 2 mg mL−1 CSP store solution. Atropine, phentolamine, and propranolol solutions were prepared immediately prior to use. Concentrations given in the results were the final concentrations of the substances in the chamber. The final concentration of DMSO in bath solutions is 0.01%. The drugs used above were purchased from Sigma Chemical Co. (St. Louis, MO, USA).

Statistical analysis

Results were expressed as mean ± standard deviation (SD). Comparisons between groups of data were made by paired and unpaired Student’s t-test. A P-value of less than 0.05 was considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References

Effects of TO extractant and CSP on GE in mice

To investigate if TO regulates gastrointestinal motility, we examined the effects of TO extractant on GE in comparison with the positive control drug, CSP. As shown in Fig. 1, EE (100 mg kg−1 bw) significantly increased the percentage of GE from the control 48.8 ± 6.1% (n = 8) to 68.0 ± 6.7% (n = 8, P < 0.01), but the potency of EE was lower than that of the positive control CSP 75.3 ± 6.5% (n = 8). Among the fractions of EE, the percentage of GE by EA and AF was 53.3 ± 6.0% (n = 9, P > 0.05) and 54.1 ± 6.3% (n = 8, P > 0.05), respectively, without significant differences compared with the control. However, BF (n = 8) produced a significant increase in GE to 86.0 ± 6.5% compared with the control (P < 0.01) and EE (P < 0.01), but had no significant difference when compared with CSP (P > 0.05). Therefore, among the fractions of EE, BF was determined to be the most effective fraction, showing a prokinetic effect like CSP.

Dose-dependent increase in GE by BF

To determine the optimal dosage, we investigated the effects of different concentrations of BF on GE in mice (n = 8 in each group; Fig. 2). The GE induced by BF at doses 0.1, 1, 10, 20, 50, and 100 mg kg−1 bw was 49.9 ± 5.1%, 51.9 ± 6.0%, 55.3 ± 6.2%, 68.4 ± 6.6%, 84.6 ± 6.4%, and 86.0 ± 6.5%, respectively. EC50 was 20.1 ± 2.2 mg kg−1. The maximum effect was observed at the dose between 50 and 100 mg kg−1 bw (Fig. 2). Therefore, the dose of 50 mg L−1 (equivalent to approximately 70 mg kg−1 bw in vivo) was used in following in vitro studies.

Effects of BF and CSP on the spontaneous smooth muscle motility of gastric fundus in rats

To investigate gastric motor mechanisms that are associated with the acceleration of GE, we examined the effect of BF (50 mg L−1) on isolated gastric smooth muscle motility. After incubation of the smooth muscle strips for approximately 30 min, spontaneous phasic motility was observed in the fundus, consistent with previous studies.17,18 After equilibration for 50 min, the phasic contractions were 0.25 ± 0.06 g (n = 12) in amplitude and 3.79 ± 0.56 cycles min−1 (n = 12) in frequency (Fig. 3). The application of BF (50 mg L−1) increased the tone by 0.68 ± 0.38 g above the basal tone (n = 6; Fig. 3A,C) and the amplitude from 0.25 ± 0.06 to 0.63 ± 0.19 g (n = 6; Fig. 3A,D), but did not significantly change the frequency from 3.88 ± 0.63 to 3.62 ± 0.98 cycles min−1 (n = 6; Fig. 3A,E). Cisapride (2 mg L−1) also increased the tone by 0.33 g ± 0.22 g above the basal tone (n = 6; Fig. 3B,C) and the amplitude from 0.24 ± 0.06 g to 0.48 ± 0.13 g (n = 6; Fig. 3B,D), but did not significantly change the frequency from 3.70 ± 0.53 to 3.55 ± 0.87 cycles min−1 (n = 6; Fig. 3B,E). These data suggest that BF can mimic the effect of CSP on the smooth muscle motility of gastric fundus, and that CSP and BF-induced increase in the contraction of gastric fundus may contribute to an increase in the intra-gastric pressure.

image

Figure 3.  Stimulatory effects of n-butanol fraction (BF) and cisapride (CSP) on smooth muscle motility of gastric fundus. Representative recordings from isolated smooth muscle strips of gastric fundus induced by BF (A) and CSP (B). Group summary data of BF and CSP-induced changes in the tone, amplitude, and frequency are shown in C, D, and E, respectively. **< 0.01 vs control (Con).

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Effects of BF and CSP on the spontaneous circular smooth muscle motility of gastric antrum in rats

As the antral smooth muscle layer in the stomach is thickest, and may play an important role in GE, we investigated the effect of BF on isolated antral smooth muscle motility. Here, we found that the application of BF enhanced the gastric antral circular smooth muscle contraction (Fig. 4A), and produced an increase in the amplitude from 0.49 ± 0.25 to 0.82 ± 0.34 g (n = 6, P < 0.05; Fig. 4A,C) and in the frequency from 4.47 ± 0.43 to 5.12 ± 0.54 cycles min−1 (n = 6, P < 0.05; Fig. 4A,D). The administration of CSP enhanced the amplitude of muscle contraction from 0.45 ± 0.21 to 0.78 ± 0.28 g (n = 6, P < 0.01, Fig. 4B,C), but did not produce significant changes in the frequency from 4.67 ± 0.48 to 4.89 ± 0.51 cycles min−1 (n = 6, P > 0.05, Fig. 4B,D). These data demonstrate that BF can enhance antral circular smooth muscle motility and may also contribute to an increase in the intra-gastric pressure.

image

Figure 4.  Stimulatory effects of n-butanol fraction (BF) and cisapride (CSP) on gastric antral circular smooth muscle motility. Representative recordings from gastric antral smooth muscle strips induced by BF (A) and CSP (B). Group summary data of BF and CSP-induced changes in the amplitude and frequency are shown in C and D, respectively. *< 0.05 vs control (Con), **< 0.01 vs Con.

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Effects of BF and CSP on the spontaneous motility of pyloric sphincter in rats

As the motility of pyloric sphincter contributes to regulating the resistance of GE, we also examined the effect of BF on the spontaneous contraction of pyloric sphincter. Here, we found that the application of BF reduced the amplitude of spontaneous contraction of pyloric sphincter from 0.53 ± 0.16 to 0.21 ± 0.15 g (n = 6, P < 0.05; Fig. 5A,B) and the frequency from 4.30 ± 0.79 to 2.75 ± 0.87 cycles min−1 (n = 6, P < 0.05; Fig. 5A,C). After washout with Tyrode solutions, spontaneous contractions of pyloric sphincter were regained (Fig. 5A). In contrast, CSP had no effects on the spontaneous motility of pyloric sphincter (n = 6, data not shown).

image

Figure 5.  Inhibitory effect of n-butanol fraction (BF) on smooth muscle motility of pyloric sphincter. A representative recording from a pyloric sphincter strip induced by BF (A). Group summary data of BF-induced decrease in the amplitude and frequency are shown in B and C, respectively. *< 0.05 vs control (Con).

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Effects of atropine, phentolamine and propranolol on increased GE by BF

To track down the possible sites of BF activity, we investigated the effects of atropine, phentolamine, and propranolol on BF-induced acceleration of GE. As shown in Fig. 6A, atropine alone significantly inhibited GE from the control 46.8 ± 6.6% to 24.6 ± 6.4% (n = 8, P < 0.01). Atropine also blocked the BF-induced increase in GE from 85.4 ± 7.1% to 27.6 ± 7.1% (n = 8, P < 0.01; Fig. 6A). Whereas phentolamine had no effect on GE from the control 48.3 ± 6.4% to 47.9 ± 7.0% (n = 8, P > 0.05; Fig. 6B), and did not alter the BF-induced increase in GE from 86.5 ± 5.5% to 84.3 ± 6.1% (n = 8, P > 0.05; Fig. 6B). Interestingly, we found that the administration of propranolol alone enhanced GE from the control group 47.8 ± 5.1% to 53.6 ± 4.4% (n = 9, P < 0.05; Fig. 6C). The combination use of propranolol and BF showed not a synergistic but an additive effect, accelerating GE from the BF group 85.8 ± 5.1% to 91.7 ± 4.5% (n = 11, P < 0.05; Fig. 6C), indicating that the enhanced GE by BF was not affected by propranolol. Taken together, these data suggest that the BF-induced increase in GE is mediated by a cholinergic pathway.

image

Figure 6.  Effects of atropine, phentolamine, and propranolol on n-butanol fraction (BF)-induced increase in gastric emptying (GE). Atropine produced a decrease in GE and blocked BF-induced increase in GE (A). The treatment with phentolamine had no effects on GE and BF-induced increase in GE (B). In contrast, propranolol produced an increase in GE. The combination of propranolol and BF showed an additive effect on GE, suggesting that BF was not affected by propranolol (C). *< 0.05 vs control (Con), **< 0.01 vs Con, #< 0.05 vs GE after BF treatment.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References

Among the fractions of TO, BF is most effective in accelerating GE. We found that the stimulatory effect of BF (100 mg kg−1 bw) on GE can mimic the effect of CSP (2 mg kg−1 bw) in mice, suggesting that BF may be used as a new prokinetic drug.

Cisapride, a representative gastrointestinal prokinetic agent, showed a high dissociation between gastrokinetic activity (0.31 mg kg−1), direct cholinergic activity (median effective dose, ED50 > 40 mg kg−1), and peripheral and central antidopamine activity (ED50: 3.3 and 18.6 mg kg−1).19 In addition, CSP produced biphasic stimulation of GE. At 10 mg kg−1, CSP inhibited GE; however, in doses ranging from 0.31 to 5 mg kg−1, CSP showed a dose-dependent stimulation of GE and the maximum excitatory effect on GE was reached from 2 to 5 mg kg−1.19 Based on the above research, CSP at the concentration of 2 mg kg−1 was employed as a positive control prokinetic drug. In this study, we found that BF also showed a dose-dependent increase in GE in vivo, and the stimulatory effect of BF (50 mg L−1) in vitro can mimic the excitatory effect of CSP (2 mg L−1), increasing the spontaneous smooth muscle motility of the gastric fundus and the antrum. These results suggest that the BF-induced increase in smooth muscle motility of the gastric fundus and antrum may contribute to an increase in the intra-gastric pressure responsible for the acceleration of GE. In addition to the intra-gastric pressure, pyloroduodenal resistance plays an important role in the regulation of GE. Here, we found that BF produced not an increase, but a decrease in the spontaneous motility of the pyloric sphincter, suggesting that the inhibitory effects of BF on pyloric smooth muscle motility may be responsible for a decrease in the resistance of GE. Taken together, all these results strongly suggest that the effect of BF on gastric motility has positional diversity, and these differential effects of BF on smooth muscle motility may cause a significant increase in GE.

Different from the BF effect, CSP had no effect on the spontaneous contraction of the pyloric sphincter and the frequency of gastric antral circular smooth muscle motility, suggesting that the regulatory mechanisms of pacemaker activities by CSP are different from those by BF. It is well known that smooth muscle cells do not show pacemaker activities in the gastrointestinal tract. At present, there is strong agreement that interstitial cells of Cajal (ICC) are the pacemaker cells that generate slow waves,20,21 which govern the frequency of the spontaneous smooth muscle contractions,21,22 resulting in normal peristalsis.23,24 It has been shown that a Ca2+-inhibited non-selective cation conductance25 and a Ca2+-activated Cl conductance26 play a role in pacemaker activities. Recently, volume-activated Cl currents are found to be present in gastric epithelial cells27 and smooth muscle cells,28 and may contribute to a depolarization of ICC and an increase in cell excitability.29 In this study, the differential effects of BF on the frequency of spontaneous motility (no change in fundus, increase in antrum) may be due to diverse regulations of these conductances expressed in different types of ICC (ICC-IM and ICC-MY). As BF produced not an increase, but a decrease in the frequency of spontaneous pyloric smooth muscle motility without influence of the smooth muscle tone, a new subtype of ICC may exist in the pyloric sphincter responsible for the different effects. Further study may be needed to unveil the mechanism of the discrepancy.

As TO has long been used as a folklore medicine to treat gastrointestinal diseases, numerous studies have attempted to isolate, characterize, and evaluate bioactive compounds in TO using high-performance liquid chromatography/electrospray ionization mass spectrometry and other chromatography techniques, and the major constituents have been identified as flavonoids, triterpenes, phytosterols, and phenolic compounds.10,30,31 Here, we focused our study on tracing down the possible sites of the effect of the most effective fraction in TO in comparison with the known mechanisms of other prokinetic agents.

Recently studied and currently available agents for treatment of gastrointestinal motor disorders include several major classes such as serotonergic agents, antidopaminergic agents, motilin receptor agonists, and ghrelin receptor agonists.32 As dopamine,33 serotonin,34 motilin,35 and ghrelin36 receptors have been shown to regulate GE partially through the direct and/or indirect cholinergic pathway, we investigate the effect of atropine on BF-induced increase in GE. The results in this study show that atropine blocked the BF-induced acceleration of GE, suggesting the involvement of a cholinergic pathway.

Several studies have shown that adrenergic receptors also play a role in the regulation of GE.37–39 Here, our results provide evidence showing that the application of phentolamine (alpha receptor antagonist) did not affect GE and BF-induced acceleration of GE. On the contrary, the application of propranolol (beta receptor antagonist) produced an increase in GE, suggesting that beta-adrenoceptors are physiologically involved in the control of GE. The combination of propranolol and BF produced an additive effect on GE, indicating that beta-adrenoceptors are not involved in the BF-induced acceleration of GE.

In summary, our studies suggest that BF-induced increase in GE is related to smooth muscle contraction. BF-induced increase in smooth muscle motility of gastric fundus and antrum may contribute to an increase in the intra-gastric pressure. BF-induced decrease in the motility of pyloric sphincter may contribute to a decrease in the resistance of food from the stomach to the small intestine. The improvement of GE by BF is predominantly mediated by an interaction between BF and the cholinergic pathway. Further study may be required to investigate the effect of pharmacologically important compounds in TO on GE and gastric smooth muscle motility.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References

This study was supported by the Yanbian University Foundation of Jilin Province, China, No. 200009.

Author Contributions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References

Y-RJ, JJ, and NGJ performed the experiments; NGJ and X-XP analyzed the data and designed the study, and NGJ wrote the manuscript; Y-RJ and JJ contributed equally to this manuscript.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. References
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