Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats

BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

Role of Enteric Glial Cells in Gastric Motility in Diabetic Rats at Different Stages

Summary： Diabetes patients tend to have the gastrointestinal motility disorder. Although the relationship between the motility disorder and both the neurons and Cajal cells in the enteric nervous system （ENS） is well established, little is known about the role of enteric glial cells （EGCs） in gastric motility in diabetes. This study aimed to examine the expression of the glial marker S100B and morphology of EGCs in gastric tissues and the relationship between activated EGCs and the damage of gastric emptying in diabetic models. The diabetic model of rat was induced with 1% streptozotocin （STZ）. The model rats at 7-14 days and at 56-63 days were defined as early diabetic rats and advanced diabetic rats, re- spectively, and normal rats at the two time periods served as their corresponding controls. The gastric emptying rate of the rats was tested by using the phenol red solution. The ultrastructure of EGCs in the gastric antrum was observed by the transmission electron microscopy, and the expression of S100B in the myenteric plexus was immunohistochemically detected. The results showed that the gastric emptying rate was significantly increased in the early diabetic rats and decreased in the advanced diabetic rats when compared with their corresponding control rats （P〈0.01 for both）. The ultrastructure of EGCs was mostly normal in both the early diabetic and control groups. Vacuolization of mitochondria and expan- sion of endoplasmic reticulum occurred in both the advanced diabetic group and its control group, and even the structure of smooth muscle cells and intestinal neurons was destroyed in the advanced diabetic group. The expression level of S100B in the advanced diabetic group was significantly decreased com- pared with its control group （P〈0.05）. It was obviously increased in the early diabetic control group when compared with the advanced diabetic control group （P〈0.05）. However, there was no significant difference in the S 100B expression between the early diabetic group and its control group （P〉0.05）. The findings suggested that the gastric motility dysfunction in diabetes may be associated with the changes of morphology and number of EGCs in the myenteric plexus.

Effects of Infrasound on Gastric Motility, Gastric Morphology and Expression of Nitric Oxide Synthase in Rat

Infrasound widely condition, productive exists in nature, our living and traffic environment. Gastrointestinal tract is relatively sensitive to infrasound. However, the effect of infrasound on gastrointestinal function is unclear. Therefore, the purpose of our study was to observe the effects of infrasound on gastric motiliW and gastric morphology and to assess the expression of nitric oxide synthase （NOS） in gastric antrum after exposure to infrasound of 8 Hz - 130 dB for 2 hours per day for 14 consecutive days. Gastric motility was assessed by gastric fluid-emptying rate. Gastric morphology was evaluated by HE. The expression of NOS was measured by tissue microarray technology. The results would contribute to understand the role of infrasound in gastroenterology, and help to explain the mechanism of infrasound on gastroenterology.

Effects and mechanisms of L-glutamate microinjected into nucleus ambiguus on gastric motility in rats

Background L-glutamate （L-GLU） is a major neurotransmitter in the nucleus ambiguus （NA）, which can modulate respiration, arterial pressure, heart rate, etc. This study investigated the effects and mechanisms of L-GLU microinjected into NA on gastric motility in rats. Methods A latex balloon connected with a pressure transducer was inserted into the pylorus through the forestomach for continuous recording of the gastric motility. The total amplitude, total duration, and motility index of gastric contraction waves within 5 minutes before microinjection and after microinjection were measured. Results L-GLU （5 nmol, 10 nmol and 20 nmol in 50 nl normal saline （PS） respectively） microinjected into the right NA significantly inhibited gastric motility, while microinjection of physiological saline at the same position and the same volume did not change the gastric motility. The inhibitory effect was blocked by D-2-amino-5-phophonovalerate （D-AP5, 5 nmol, in 50 nl PS）, the specific N-methyI-D-aspartic acid （NMDA） receptor antagonist, but was not influenced by 6-cyaon-7-nitroquinoxaline-2,3-（1H,4H）-dione （CNQX） （5 nmol, in 50 nl PS）, the non-NMDA ionotropic receptor antagonist. Bilateral subdiaphragmatic vagotomy abolished the inhibitory effect by microinjection of L-GLU into NA. Conclusions Microinjection of L-GLU into NA inhibits the gastric motility through specific NMDA receptor activity, not non-NMDA receptor activity, and the efferent pathway is the vagal nerves.

Effect of grouped ST36 or RN12 on gastric motility and sensation

Objective: To investigate the effects of paired ST36 and RN12 acupuncture stimulation on gastric motility and the firing rate of responsible neurons in anesthetized rats.Methods: Using electrophysiological methods, we measured the effects of acupuncture at RN12, ST36, or RN12+ST36 on gastric motility as well as nerve discharges from the gastric sympathetic, vagal nerve, and wide dynamic range(WDR) neurons in the spinal dorsal horn T7-9 in anesthetized rats.Results: 1) Acupuncture at RN12 inhibited gastric motility(83.84±4.49)% and vagal nerve discharge(65.64±5.67)%, but promoted sympathetic nerve activity(243.70±40.67)%; acupuncture at ST36 induced opposing effects on gastric motility(111.31±2.01)% and vagal nerve discharge(166.98±15.92)%. Interestingly, acupuncture at RN12+ST36 together yielded effects similar to that of acupuncture at RN12 alone(93.59±2.05)%,(54.52±7.12)%. 2) WDR neuron discharges induced by gastric distension were inhibited by acupuncture at RN12(194.56 ±18.79)%. However, acupuncture at ST36 induced a more significant inhibitory effect.Conclusion: Acupuncture at RN12 inhibits gastric motility by activation of the sympathetic reflex at the spinal level; acupuncture at ST36 promotes gastric motility by activation of the parasympathetic reflex at the supraspinal level, and acupuncture at RN12+ST36 produces a similar decrease in gastric motility as RN12 stimulation alone. Both acupoints decrease the effect of noxious gastric distention on WDR neuron activity, but paired RN12+ST36 stimulation does not significantly affect WDR neuron discharge.

Xiangbinfang granules enhance gastric antrum motility via intramuscular interstitial cells of Cajal in mice

BACKGROUND Interdigestive migrating motor complexes(MMC)produce periodic contractions in the gastrointestinal tract,but the exact mechanism of action still remains unclear.Intramuscular interstitial cells of Cajal(ICC-IM)participate in gastrointestinal hormone and neuromodulation,but the correlation between ICCIM and MMC is also unclear.We found that xiangbinfang granules(XBF)mediated the phase III contraction of MMC.Here,the effects of XBF on gastric antrum motility in W/Wv mice and the effects of ICC-IM on gastric antrum MMC are reported.AIM To observe the effects of ICC-IM on gastric antrum motility and to establish the mechanism of XBF in promoting gastric antrum motility.METHODS The density of c-kit-positive ICC myenteric plexus(ICC-MP)and ICC-IM in the antral muscularis of W/Wv and wild-type(WT)mice was examined by confocal microscopy.The effects of XBF on gastric antrum slow waves in W/Wv and WT mice were recorded by intracellular amplification recording.Micro-strain-gauge force transducers were implanted into the gastric antrum to monitor the MMC and the effect of XBF on gastric antrum motility in conscious W/Wv and WT mice.RESULTS In the gastric antrum of W/Wv mice,c-kit immunoreactivity was significantly reduced,and no ICC-IM network was observed.Spontaneous rhythmic slow waves also appeared in the antrum of W/Wv mice,but the amplitude of the antrum slow wave decreased significantly in W/Wv mice(22.62±2.23 mV vs 2.92±0.52 mV,P<0.0001).MMCs were found in 7 of the 8 WT mice but no complete MMC cycle was found in W/Wv mice.The contractile frequency and amplitude index of the gastric antrum were significantly increased in conscious WT compared to W/Wv mice(frequency,3.53±0.18 cpm vs 1.28±0.12 cpm;amplitude index,23014.26±1798.65 mV·20 min vs 3782.16±407.13 mV·20 min;P<0.0001).XBF depolarized smooth muscle cells of the gastric antrum in WT and W/Wv mice in a dose-dependent manner.Similarly,the gastric antrum motility in WT mice was significantly increased after treatment with XBF 5 mg(P<0.05).Atropine(0.1 mg/kg)blocked the enhancement of XBF in WT and W/Wv mice completely,while tetrodotoxin(0.05 mg/kg)partially inhibited the enhancement by XBF.CONCLUSION ICC-IM participates in the regulation of gastric antrum MMC in mice.XBF induces MMC III-like contractions that enhance gastric antrum motility via ICCIM in mice.

Can adiponectin have an additional effect on the regulation of food intake by inducing gastric motor changes?

The regulation of food intake is a complex mechanism,and the hypothalamus is the main central structure implicated.In particular,the arcuate nucleus appears to be the most critical area in the integration of multiple peripheral signals.Among these signals,those originating from the white adipose tissue and the gastrointestinal tract are known to be involved in the regulation of food intake.The present paper focuses on adiponectin,an adipokine secreted by white adipose tissue,which is reported to have a role in the control of feeding by acting centrally.The recent observation that adiponectin is also able to influence gastric motility raises the question of whether this action represents an additional peripheral mechanism that concurs with the central effects of the hormone on food intake.This possibility,which represents an emerging aspect correlating the central and peripheral effects of adiponectin in the hunger-satiety cycle,is discussed in the present paper.

Glucagon-like peptide-2 modulates the nitrergic neurotransmission in strips from the mouse gastric fundus

AIM To investigate whether glucagon-like peptide-2(GLP-2) influences the neurally-induced responses in gastric strips from mice, since no data are available. METHODS For functional experiments, gastric fundal strips were mounted in organ baths containing Krebs-Henseleit solution. Mechanical responses were recorded via forcedisplacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparationwas threaded. The effects of GLP-2(2 and 20 nmol/L) were evaluated on the neurally-induced contractile and relaxant responses elicited by EFS. Neuronal nitric oxide synthase(n NOS) enzyme was evaluated by immunohistochemistry.RESULTS In the functional experiments, electrical field stimulation(EFS, 4-16 Hz) induced tetrodotoxin(TTX)-sensitive contractile responses, which were reduced in amplitude by GLP-2(P < 0.05). In the presence of the nitric oxide(NO) synthesis inhibitor L-NNA, GLP-2 no longer influenced the neurally-evoked contractile responses(P > 0.05). The direct smooth muscle response to methacholine was not influenced by GLP-2(P > 0.05). In the presence of guanethidine and carbachol, the addition of GLP-2 to the bath medium evoked TTX-sensitive relaxant responses that were unaffected by L-NNA(P > 0.05). EFS induced a fast NO-mediated relaxation, whose amplitude was enhanced in the presence of the hormone(P < 0.05). Immunohistochemical experiments showed a significant increase(P < 0.05) in n NOS immunoreactivity in the nerve structures after GLP-2 exposure. CONCLUSION The results demonstrate that in gastric fundal strips, GLP-2 influences the amplitude of neurally-induced responses through the modulation of the nitrergic neurotransmission and increases n NOS expression.

Dynamic carbon 13 breath tests for the study of liver function and gastric emptying

In gastroenterological practice,breath tests(BTs)are diagnostic tools used for indirect,non-invasive assessment of several pathophysiological metabolic processes,by monitoring the appearance in breath of a metabolite of a specific substrate.Labelled substrates originally employed radioactive carbon 14(^(14)C)and,more recently,the stable carbon 13 isotope(^(13)C)has been introduced to label specific substrates.The ingested^(13)C-substrate is metabolized,and exhaled^(13)CO_(2)is measured by mass spectrometry or infrared spectroscopy.Some^(13)C-BTs evaluate specific(microsomal,cytosolic,and mitochondrial)hepatic metabolic pathways and can be employed in liver diseases(i.e.simple liver steatosis,non-alcoholic steato-hepatitis,liver fibrosis,cirrhosis,hepatocellular carcinoma,drug and alcohol effects).Another field of clinical application for^(13)C-BTs is the assessment of gastric emptying kinetics in response to liquids(^(13)C-acetate)or solids(^(13)C-octanoic acid in egg yolk or in a pre-packed muffin or the^(13)C-Spirulina platensis given with a meal or a biscuit).Studies have shown that^(13)C-BTs,used for gastric emptying studies,yield results that are comparable to scintigraphy and can be useful in detecting either delayed-(gastroparesis)or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects.Thus,^(13)C-BTs represent an indirect,cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease,and several other potential applications are being studied.

Effects of Sijunzi Dripping Pill on Gastrointestinal Motility of Mice

Objective To study the effects of Sijunzi Dripping Pill（SDP）on gastrointestinal motilityof mice.Methods The diarrhea and swimming model of mice was made by Rhei Radixet Rhizoma-induced spleen deficiency.The intestinal transit,gastric emptying test,serum motilin（MTL）,vasoactive intestinal peptide（VIP）,and substance P（SP）were chosen to observe the effects of high-,mid-,and low-dose SDP on stomach movements,and the water extractive of Sijunzi Decoction was used as positive control.Results Compared with the control group,the gastric emptying rate in the gastrointestinal motility group was significantly decreased,the intestinal propulsion rate was obviously increased,the levels of MTL,prostaglandin E2（PGE2）,and SP were increased（P〈0.05）,while the level of VIP was decreased（P〈0.05）.Compared with the model group,SDP could decrease the intestinal transit rate,whereas increase the gastric emptying rate and the level of MTL（P〈0.05）;The high-dose SDP could decrease the level of PGE2（P〈0.05）and the low-dose SDP could decrease the level of VIP（P〈0.05）;Each group had no significant effect on SP.Conclusion SDP has the good effect on increasing the gastrointestinal motility of mice,and its function may partly relate to the regulation of the levels of MTL and VIP as well as PGE2.