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Song J.,University of Texas Medical Branch | Yin J.,University of Texas Medical Branch | Chen J.D.Z.,University of Texas Medical Branch | Chen J.D.Z.,Ningbo Pace Translational Medical Research Center
Neurogastroenterology and Motility | Year: 2013

Background: Antidepressants are commonly used for treating functional gastrointestinal (GI) diseases. However, little is known whether antidepressants improve or impair GI motility. This study aimed at exploring possible effects of a serotonin-norepinephrine reuptake inhibitor, desvenlafaxine succinate (DVS), on GI motility in dogs. Methods: Eight dogs chronically implanted with a duodenal cannula and a colon cannula were used in the study. Experiments were performed to assess the effects of a single dose of DVS (50 or 100 mg) and DVS given 50 mg once a day for 2 weeks on gastric emptying of solid, small intestinal transit, and colon transit and contractions. Key Results: (1) DVS significantly delayed gastric emptying of solid at a single dose of 50 or 100 mg. The inhibitory effect on gastric emptying was completely blocked by guanethidine (an adrenergic blocking agent). (2) DVS at a single dose of 50 or 100 mg accelerated colon transit, but showed no effects on small bowel transit. (3) DVS at a single dose of 50 mg enhanced colon contractions and guanethidine blocked the effect. (4) Surprisingly, DVS given at 50 mg once daily for 2 weeks did not alter gastric emptying, small bowel transit or colon transit. Conclusions & Inferences: Acute DVS delays gastric emptying of solid and enhances the contractions of the colon, which may be mediated via the sympathetic mechanism. Acute DVS promotes the transit of the colon but not the small intestine. However, chronic administration of DVS does not seem to alter GI motility. © 2013 John Wiley & Sons Ltd.


Song J.,University of Texas Medical Branch | Song J.,Huazhong University of Science and Technology | Yin J.,University of Texas Medical Branch | Sallam H.S.,University of Texas Medical Branch | And 4 more authors.
Neurogastroenterology and Motility | Year: 2013

Background: Delayed gastric emptying (GE) is common in patients with severe burns. This study was designed to investigate effects and mechanisms of electroacupuncture (EA) on gastric motility in rats with burns. Methods: Male rats (intact and vagotomized) were implanted with gastric electrodes, chest and abdominal wall electrodes for investigating the effects of EA at ST-36 (stomach-36 or Zusanli) on GE, gastric slow waves, autonomic functions, and plasma interleukin 6 (IL-6) 6 and 24 h post severe burns. Key Results: (i) Burn delayed GE (P < 0.001). Electroacupuncture improved GE 6 and 24 h post burn (P < 0.001). Vagotomy blocked the EA effect on GE. (ii) Electroacupuncture improved burn-induced gastric dysrhythmia. The percentage of normal slow waves was increased with EA 6 and 24 h post burn (P = 0.02). (iii) Electroacupuncture increased vagal activity assessed by the spectral analysis of heart rate variability (HRV). The high-frequency component reflecting vagal component was increased with EA 6 (P = 0.004) and 24 h post burn (P = 0.03, vs sham-EA). (iv) Electroacupuncture attenuated burn-induced increase in plasma IL-6 at both 6 (P = 0.03) and 24 h post burn (P = 0.003). Conclusions & Inferences: Electroacupuncture at ST-36 improves gastric dysrhythmia and accelerates GE in rats with burns. The improvement seems to be mediated via the vagal pathway involving the inflammatory cytokine IL-6. © 2013 John Wiley & Sons Ltd.


Song J.,University of Texas Medical Branch | Song J.,Huazhong University of Science and Technology | Yin J.,University of Texas Medical Branch | Xu X.,Ningbo Pace Translational Medical Research Center | And 2 more authors.
American Journal of Translational Research | Year: 2015

Objective: To systemically explore effects of large dose of lubiprostone on gastrointestinal (GI) transit and contractions and its safety in dogs. Methods: 12 healthy dogs were studied. 6 dogs were operated to receive duodenal cannula and colon cannula and the other 6 dogs received gastric cannula. Lubiprostone was orally administrated at a dose of 24 μg or 48 μg 1 hr prior to the experiments. Gastric emptying (GE) of solids and small bowel transit were evaluated by collecting the effluents from the duodenal cannula and from the colon cannula. Gastric accommodation was measured by barostat. Gastric and intestinal contractions were by manometry. Colon transit was by X-ray pictures. Results: 1) Lubiprostone 48 μg not 24 μg accelerated GE. Atropine could block the effect; 2) Average motility index (MI) of gastric antrum in lubiprostone 48 μg session was significantly higher in both fasting state (P = 0.01) and fed state (P = 0.03). Gastric accommodation was not significantly different; 3) Lubiprostone 48 μg accelerated small bowel and colon transit. Atropine could block the effect on small bowel transit; 4) Lubiprostone 48 μg increased postprandial small bowel MI (P = 0.0008) and colon MI (P = 0.002). 5) No other adverse effects except for diarrhea were observed. Conclusion: Acute administration of lubiprostone at a dose of 48 μg accelerates GI motility and enhances GI contractions in the postprandial state. The findings suggest that lubiprostone may have an indirect prokinetic effects on the GI tract and vagal activity may be involved. Lubiprostone may be safely used. © 2015, E-Century Publishing Corporation. All right reserved.


Li S.,Oklahoma Medical Research Foundation | Chen J.D.Z.,Oklahoma Medical Research Foundation | Chen J.D.Z.,Johns Hopkins University | Chen J.D.Z.,Ningbo Pace Translational Medical Research Center
Neurogastroenterology and Motility | Year: 2014

Background: Although without evidence of organic structural abnormalities, pain or discomfort is a prominent symptom of functional dyspepsia and considered to reflect visceral hypersensitivity whose underlying mechanism is poorly understood. Here, we studied electrophysiological properties and expression of voltage-gated potassium channels in dorsal root ganglion (DRG) neurons in a rat model of functional dyspepsia induced by neonatal gastric irritation. Methods: Male Sprague-Dawley rat pups at 10-day old received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6 days and studied at adulthood. Retrograde tracer-labeled gastric-specific T8-T12 DRG neurons were harvested for the patch-clamp study in voltage and current-clamp modes and protein expression of K+ channel in T8-T12 DRGs was examined by western blotting. Key Results: (1) Gastric specific but not non-gastric DRG neurons showed an enhanced excitability in neonatal IA-treated rats compared to the control: depolarized resting membrane potentials, a lower current threshold for action potential (AP) activation, and an increase in the number of APs in response to current stimulation. (2) The current density of tetraethylammonium insensitive (transiently inactivating A-type current), but not the tetraethylammonium sensitive (slow-inactivating delayed rectifier K+ currents), was significantly smaller in IA-treated rats (65.4 ± 6.9 pA/pF), compared to that of control (93.1 ± 8.3 pA/pF). (3) Protein expression of KV4.3 was down-regulated in IA-treated rats. Conclusions & Inferences: A-type potassium channels are significantly down-regulated in the gastric-specific DRG neurons in adult rats with mild neonatal gastric irritation, which in part contribute to the enhanced DRG neuron excitabilities that leads to the development of gastric hypersensitivity. © 2014 John Wiley & Sons Ltd.


Li S.,Oklahoma Medical Research Foundation | Chen J.D.Z.,Oklahoma Medical Research Foundation | Chen J.D.Z.,Ningbo Pace Translational Medical Research Center | Chen J.D.Z.,Johns Hopkins University
Neurogastroenterology and Motility | Year: 2014

Background: Diabetic gastroparesis (delayed gastric emptying) is associated with antral hypomotility. L-type Ca2+ channels play an important role in generation of action potentials and activation of contractions. This study was designed to investigate if the function of the L-type Ca2+ channels of antral circular smooth muscle cells (SMCs) is impaired in streptozotocin (STZ)-induced diabetic rats. Methods: Eight weeks after the injection of STZ or vehicle, whole-cell patch clamp was used to record Ca2+ currents, and isometric tension recording was used to measure Ca2+ influx-induced contractions in circular muscle strips. Solid gastric emptying was measured in diabetic and control rats. Protein expression of Ca2+αlC-subunit in antral smooth muscles was compared between diabetic and control rats. Key Results: (1) Solid gastric emptying, independent of age or bodyweight, was slower in the diabetic rats, even after acute correction of hyperglycemia. (2) Verapamil, a potent calcium channel blocker, dose dependently reduced solid gastric emptying in normal rats. (3) Current density of L-type Ca2+ channel at 10 mV in antral circular SMCs was significantly decreased in the diabetic rats (-9.8 ± 0.7 pA/pF vs -15.9 ± 1.0 pA/pF in control, p < 0.001). However, protein expression of the Ca2+ channel in antral muscles did not differ between diabetic and control rats. (4) Contractile responses to 1 and 3 mM [Ca2+] were significantly reduced in the diabetic antral circular muscle strips, indicative of reduced Ca2+ influx. Conclusions & Inferences: These data suggested that the decreased L-type Ca2+ current in antral SMCs may contribute to antral hypomotility in STZ-induced diabetic rats. © 2014 John Wiley & Sons Ltd.

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