Activity Of Gastric Smooth Muscle Research Articles

Effects of Chinese ginger Alpinia officinarum-based phytopharmaceutical compound on gastric motility

BackgroundAlpinia officinarum, better known as Chinese ginger, is used for the treatment of gastrointestinal disorders in traditional Chinese and Ayurveda medicine. However, scientific evidence of an effect on gastrointestinal motility is missing. PurposeThis study aimed to estimate the effect of a phytopharmaceutical compound (PPC) based on Alpinia officinarum on gastric motility in vitro in order to assess its potential use in the treatment of functional dyspepsia. Study DesignWe investigated to which extent the compound affects the activity of gastric smooth muscle and we identified involved mediating cellular mechanisms. MethodsBasal and stimulated muscle activity were recorded from muscle-myenteric plexus preparations from three different regions of the guinea pig stomach before and after incubation with different concentrations of the PPC in an organ bath setup. Effect-mediating mechanisms were investigated by pharmacology. ResultsPPC exhibited a smooth muscle relaxation in a concentration-dependent manner. This was region- and muscle type specific as it was greater in fundus and corpus than in antrum and more pronounced in the circular than in the longitudinal muscle layer. The effect was primarily myogenic and at least partly mediated by TRPA1. ConclusionThe investigated PPC reduces basal tone particularly of fundus smooth muscle in a non-neuronal manner by inhibiting calcium influx via TRPA1, without affecting antral motility. Based on these data, Alpinia officinarum could be considered for phytopharmaceutical treatment of functional dyspepsia.

Evidence that resistin acts on the mechanical responses of the mouse gastric fundus

Resistin, among its several actions, has been reported to exert central anorexigenic effects in rodents. Some adipokines which centrally modulate food intake have also been reported to affect the activity of gastric smooth muscle, whose motor responses represent a source of peripheral signals implicated in the control of the hunger-satiety cycle through the gut-brain axis. On this basis, in the present experiments, we investigated whether resistin too could affect the mechanical responses in the mouse longitudinal gastric fundal strips. Electrical field stimulation (EFS) elicited tetrodotoxin- and atropine-sensitive contractile responses. Resistin reduced the amplitude of the EFS-induced contractile responses. This effect was no longer detected in the presence of L-NNA, a nitric oxide (NO) synthesis inhibitor. Resistin did not influence the direct muscular response to methacholine. In the presence of carbachol and guanethidine, EFS elicited inhibitory responses whose amplitude was increased by resistin. L-NNA abolished the inhibitory responses evoked by EFS, indicating their nitrergic nature. In the presence of L-NNA, resistin did not have any effect on the EFS-evoked inhibitory responses. Western blot and immunofluorescence analysis revealed a significant increase in neuronal nitric oxide synthase (nNOS) expression in neurons of the myenteric plexus following resistin exposure. In conclusion, the present results offer the first evidence that resistin acts on the gastric fundus, likely through a modulatory action on the nitrergic neurotransmission.

Ability of 2-Chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide to Stimulate Endogenous Nitric Oxide Synthesis

Papaverine is one of the isoquinoline alkaloids derived from opium which is a vasodilator and smooth muscle relaxant. Using its chemical structure as a basic model, we synthesized 2-chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide as an isoquinoline precursor (IQP). Aim: Clarifying the nature of the relationship between IQP as a new biologically active molecule and the neurotransmitters acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5-HT), as well as with the nitric oxide (NO). Materials and methods: The IQP compound was tested on the isolated gastric smooth muscle preparations (SMPs) from rats to determine its effects on spontaneous contractile activity. NO concentration in tissue homogenates was determined, and immunohistochemistry was used to visualize the expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in smooth muscle (SM) cells. Results: The data from the isometric measurements suggest that IQP has an additional specific action affecting the intracellular signaling pathways of 5-HT. Using immunohistochemistry, we found that the combination of 5-HT and IQP affected the density and intensity of nNOS-positive cells, which increase significantly in the myenteric plexus and SM cells. Conclusions: In conclusion, IQP is involved in the regulation of intestinal neurons expressing nNOS, affects the function of nNOS/NO, and, by this mechanism, probably regulates the spontaneous contractile activity of gastric SM.

The influence of a simulated digest of an equine dietary feed additive G's formula on contractile activity of gastric smooth muscle in vitro.

G's Formula is a novel equine feed additive formulated to promote optimal GI function. The objective of this study was to determine whether the addition of a simulated digest of the composite feed additive G's Formula (FA) would alter the contractile response of gastric smooth muscle to acetylcholine (Ach). Smooth muscle strips from porcine stomachs were excised and attached to an isometric force transducer. An experiment was run to compare tissue contraction between tissue exposed to FA (FA; n=8, simulated digest of FA was added to the bath) and control tissue (CO; n=8, no additions made). Increasing concentrations of Ach were added into the bath such that the concentration increased from 10-8 -10-3 M. Based on the analysis of these data, a difference between FA and CO was observed. Therefore, another trial was run which included a blank group (BL n=6) in which the tissue was exposed to the simulated digest without FA. More CO (n=5) and FA (n=4) tissue was also run. Force was compared to baseline and between groups. In FA group, mean force for 1-min following all Ach additions was higher than baseline (p<.05) and by 2-min the integral-under-force/time curve (AUC) was higher than baseline from 10-7 -10-3 M compared to lower concentrations of Ach in both CO (10-6 M for both) and BL (10-5 M and 10-6 M, respectively). By 8-min AUC of all Ach concentrations were higher than baseline in FA compared to an Ach of 10-6 M in both CO and BL. A simulated digest of FA appears to sensitize gastric smooth muscle to Ach in vitro. FA may increase GI contractility, and the functional effect of this should be studied further in vivo.

Roles of prostaglandin E2-EP1 receptor signaling in regulation of gastric motor activity and emptying

It is widely accepted that the inhibition of gastric motor activity as well as the maintenance of gastric mucosal blood flow and mucous secretion are important for the homeostasis of the gastric mucosa. The present study was performed to ascertain whether or not endogenous PGs, which can protect the stomach from noxious stimuli, affect gastric motor activity and emptying. The myoelectrical activity of rat gastric smooth muscle was increased at intragastric pressures of over 2 cmH(2)O. Replacement of intragastric physiological saline with 1 M NaCl solution significantly increased PGI(2) and PGE(2) in stomach and suppressed the myoelectrical activity under a pressure of 2 cmH(2)O by 70%. Indomethacin inhibited the suppression of myoelectrical activity by 1 M NaCl. The myoelectrical activity under a pressure of 2 cmH(2)O was suppressed by continuous infusion of a selective EP1 agonist (ONO-DI-004, 3-100 nmol·kg(-1)·min(-1)) into the gastric artery in a dose-dependent manner, but not by that of the PGI receptor agonist beraprost sodium (100 nmol·kg(-1)·min(-1)). Suppression of myoelectrical activity with 1 M NaCl was inhibited by continuous infusion of a selective EP1 antagonist (ONO-8711, 100 nmol·kg(-1)·min(-1)) into the gastric artery. Furthermore, gastric emptying was tested in EP1 knockout mice and their wild-type counterparts. Gastric emptying was strongly suppressed with intragastric 1 M NaCl in wild-type mice, but this 1 M NaCl-induced suppression was not seen in EP1 knockout mice. These results suggest that PGE(2)-EP1 signaling has crucial roles in suppression of myoelectrical activity of gastric smooth muscles and inhibition of gastric emptying and that EP1 is an obvious target for drugs that control gastric emptying.

Calcitonin gene‐related peptide released by capsaicin suppresses myoelectrical activity of gastric smooth muscle

It is widely accepted that the inhibition of gastric motor activity as well as the maintenance of gastric mucosal blood flow and mucous secretion are important for the homeostasis of the gastric mucosa. The present study was performed to ascertain whether or not capsaicin, which can protect the stomach from noxious stimuli, affects gastric motor activity. Male Sprague-Dawley rats were anesthetized with urethane, and the stomach was cannulated by two catheters from esophageal and duodenal sides. A biopolar electrode was fixed to the serosal surface of the antrum and myoelectrical activity was recorded during the instillation of a small volume of solutions. The myoelectrical activity of rat gastric smooth muscle was increased at intragastric pressures of >2 cmH(2)O. Replacement of intragastric physiological saline with 1.6 mmol/L capsaicin solution significantly suppressed this myoelectrical activity by 50%. Intragastric capsaicin administration caused a significant release of substance P (SP) and calcitonin gene-related peptide (CGRP). The maximum released levels of CGRP in the gastric perfusates were 100-fold those of SP. The myoelectrical activity observed at an intragastric pressure of 2 cmH(2)O was avoided by continuous infusion of CGRP (0.1-3.0 nmol/kg per min) into the gastric artery in a dose-dependent manner, but not by that of SP (1.0 nmol/kg per min). Continuous CGRP-(8-37) infusion into the gastric artery completely blocked the reduction by intragastric capsaicin of myoelectrical activity. These results suggest that the suppression of the myoelectrical activity of gastric smooth muscle by capsaicin is attributable to the endogenous CGRP released.

Cyclooxygenase inhibition in the dorsal vagal complex of the rat evokes increases in gastric motor function

To characterize the involvement of brainstem cyclooxygenase (COX) in the vagal control of gastric motor function, tolmetin, a reversible COX inhibitor, was applied to the surface of the dorsal medulla oblongata or microinjected into the dorsal vagal complex (DVC) in β-chloralose anesthetized rats, while intragastric pressure and contractile activity of the pyloric circular and greater curvature longitudinal muscle were monitored. Tolmetin, applied to the surface of the medulla oblongata, increased intragastric pressure and stimulated contractile activity of gastric smooth muscle. Comparable gastric motor effects were observed after microinjection of tolmetin into the DVC. All the effects of tolmetin were abolished by bilateral vagotomy at the midcervical level. These results demonstrate for the first time that COX inhibition evokes vagally-mediated gastric motor effects in the DVC of the rat and support a role for COX products in gastrointestinal regulation.

Suppression of myoelectrical activity of gastric smooth muscle by endogenous gastric prostaglandin E2.

The myoelectrical activity of the gastric smooth muscle, recorded by a bipolar electrode placed at the gastric antrum in rats, could be recorded when the stomach was distended with 5 ml of physiological saline. This activity may be induced by a mucosal reflex and was inhibited both by atropine and by pirenzepine. Replacement of physiological saline with solutions of NaCl suppressed this myoelectrical activity. This suppression was dependent on the concentrations of NaCl in the solutions, from 0.3 to 1.0 M. Pretreatment with indomethacin (10 mg/kg, intravenous) completely prevented this suppression induced by different concentrations of NaCl solutions. Intragastric administration of 1.0 M NaCl in solution caused an increase in the levels of PGE2 in the gastric lumen. Intragastric administration of OU-1308, a synthetic derivative of PGE1, also suppressed the myoelectrical activity in a dose-dependent manner. It is concluded that the suppression of gastric myoelectrical activity by hyperosmolar NaCl may be attributable to the generation of endogenous PGE2 in the stomach.