Central and peripheral action of GABAA and GABAB agonists on small intestine motility in rats

Fargeas, M. J.; Fioramonti, Jean; Buéno, Lionel

doi:10.1016/0014-2999(88)90763-7

Cited by 35 publications

(18 citation statements)

References 26 publications

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“…Centrally mediated effects of GABAB receptor activation on the gastrointestinal system include an increase in gastric motility (Andrews, Bingham & Wood, 1987;Fargeas, Fioramonti & Bueno, 1988), increased gastric corpus pressure (Andrews et al 1987) and stimulation of gastric acid secretion (Goto, Tache, Debas & Novin, 1985). Baclofen decreased phrenic nerve activity and blockade of GABAB receptors by phaclofen, increased phrenic nerve activity, and decreased inspiratory duration (Schmidt, Bohmer & Gebauer, 1989).…”

Section: Introductionmentioning

confidence: 99%

The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.

Brooks

Glaum

Miller

et al. 1992

The Journal of Physiology

113

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SUMMARY1. Intracellular and whole-cell patch recordings were made from sixty-seven neurones located in the nucleus tractus solitarii (NTS) in transverse slices of rat brainstem.2. Baclofen at concentrations of 2-20 ftM caused hyperpolarization from normal resting membrane potentials (Vm). This response was associated with a decrease in input resistance (Rm) tested by current pulses in discontinuous current clamp mode when membrane potential was restored to control level by current injection. In single electrode discontinuous voltage clamp mode, baclofen'at these concentrations caused a small (< 50 pA) outward current associated with increased membrane conductance measured by voltage steps from holding potentials (Vh) of -50 or -60 mV. Current-voltage relations at these Vhs and the results of varying Vh between -50 and -110 mV during responses to baclofen gave a reversal potential of -73 mV. The amplitudes of baclofen responses were related to K+ concentration tested by comparing responses in media containing 1-24 mm extracellular K', indicating that postsynaptically baclofen acts via a K+ conductance.3. These effects were still apparent in the presence of tetrodotoxin (which did not abolish all spontaneous synaptic activity) and also in medium containing a combination of C02+, the excitatory amino acid antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the GABAA antagonist bicuculline which blocked synaptic activity.4. The amplitude and frequency of spontaneous postsynaptic potentials (spPSPs) and spontaneous postsynaptic currents (spPSCs) were reduced by baclofen at concentrations (1 /LM or less) which had no effect on membrane potential or holding current in current or voltage clamp recordings respectively.5. The amplitude of evoked excitatory (evEPSPs/evEPSCs) and inhibitory (evIPSPs/evIPSCs) synaptic events elicited by electrical stimulation in the vicinity of the tractus solitarius (TS) was reduced by low concentrations of baclofen (250 nM-1 jM) which did not produce discernible postsynaptic responses.6. In order to examine the effects of baclofen on excitatory synaptic events MS 9797 P. A. BROOKS AND OTHERS without contamination with inhibitory events, stimulation of the TS was carried out in the presence of bicuculline. Conversely to investigate actions on purely inhibitory synaptic responses experiments were carried out with CNQX in the bathing solution. Inhibitory synaptic responses could still be evoked, presumably by stimulation of interneurones in the vicinity of the TS. IPSPs/IPSCs were more sensitive to baclofen than EPSPs/EPSCs.7. The effects of baclofen on membrane potential or holding current and PSP/PSCs were antagonized by 2-hydroxysaclofen (400 /M) confirming that baclofen was acting at y-aminobutyric acid (GABA)B receptors.8. The pre-and postsynaptic depressant effects of baclofen are discussed in relation to the physiological effects of baclofen application in vivo.

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Section: Introductionmentioning

confidence: 99%

The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.

Brooks

Glaum

Miller

et al. 1992

The Journal of Physiology

113

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“…However, we may speculate that, if this drug interferes with the intermittent motor activity of this region, as described for the LES, the increased frequency or duration of pylorus contractions may compromise the GE of solids. A second hypothesis could be that the increased duodenal contractions induced by baclofen (16) , in opposition to its effect on the increase of gastric contraction (1) , would impair the GE of a solid meal such as that used in the present study. These hypotheses should be tested by means of experiments specifically planned for this purpose.…”

Section: Discussionmentioning

confidence: 88%

“…The effect on gastric tonus is produced by the levo(-)-enantiomer of baclofen (1) . Baclofen, a highly lipophilic compound, easily crosses the blood brain barrier (16) . The ICV dose (~ 8 mg/kg), which significantly increased GE, was 250 times lower than the highest dose administered IV (2000 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

“…The use of GABA agonists and antagonists for receptors located in the DVC neurons has shown that this acid is involved in the control of gastrointestinal motility (3,19,38,46) . In particular, baclofen, through the vagus nerve, blocks the inhibitory stimuli on gastric secretion and increases gastric tonus and the frequency and amplitude of gastric and duodenal contractions (1,16,18,31) . In a study on the effect of baclofen on GE in mice, the drug, when administered intraperitoneally (IP) accelerated the GE of solids and delayed the GE of liquid, suggesting different effects on the proximal (liquid GE) and the distal (solid GE) stomach (40) .…”

Section: Arq Gastroenterol 291 V 47 -No3 -Jul/set 2010mentioning

confidence: 99%

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Effect of baclofen on liquid and solid gastric emptying in rats

Collares

Vinagre

2010

Arq. Gastroenterol.

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-Context -Gamma-aminobutyric acid (GABA) is a potent inhibitory neurotransmitter. There is evidence that GABA B receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. Objectives -To assess the intracerebroventricularly (ICV) and intravenously (IV) effect of baclofen, a GABA B receptor agonist, on liquid and solid gastric emptying in rats. Methods -Adult male Wistar rats weighing 250-300 g (n = 6-8 animals) were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention (%GR) 10 and 15 min after orogastric administration of saline and 10% glucose meals, respectively. Baclofen was injected ICV (1 and 2 mg/animal) through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg) into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 mg/animal) or IV (1 and 2 mg/kg) immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution) ICV or IV.Results -The group of animals receiving baclofen ICV (2 mg/animal) presented a significantly lower (P<0.05, Tukey test) %GR (mean ± SEM) of the saline (18.1 ± 2.5%) compared to control (33.2 ± 2.2%). In the group receiving the drug IV, the gastric retention of the same test meal did not differ from control. ICV and IV administration of baclofen had no effect on the gastric emptying of the 10% glucose solution compared to control. ICV administration of 1 or 2 mg baclofen/animal significantly increased the gastric retention of the solid test meal (57.9 ± 6.5% and 66.6 ± 6.3%, respectively) compared to control (35.1 ± 4.4%). The same phenomenon was observed only with the IV dose of 2 mg/kg (71.9 ± 2.6%) compared to control (52.7 ± 2.8%). Conclusions -Baclofen administered: 1. ICV (2 mg/animal), but not IV, increased gastric emptying of a non-caloric isotonic liquid test meal (saline); 2. when administered ICV or IV, it had no effect of gastric emptying of a 10% glucose solution; 3) when administered ICV (1 and 2 mg/animal) and IV (2 mg/kg) it delayed the gastric emptying of the solid meal. HEADINGS -Gastric emptying. Baclofen. Rats.

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“…It is reported that baclofen (GABA-B agonist) may alleviate the inhibitory effect of exogenous peripheral cholecystokinin (CCK), a peptide hormone that plays important roles as gastrointestinal hormone and neurotransmitter, on dry matter intake (DMI) in rats (Ebenezer, 1995), indicating that GABA and CCK may have associative effects on DMI. Moreover, motility in duodenum can be inhibited by activating GABA-A receptor, or be activated by stimulating GABA-B receptor (Fargeas et al, 1988). In contrast, motility in ileum can be activated by stimulating GABA-A receptor, or be restrained by activation of GABA-B receptor (Ong and Kerr, 1982).…”

Section: Introductionmentioning

confidence: 99%

Effects of γ-aminobutyric acid on feed intake, growth performance and expression of related genes in growing lambs

Wang

Chacher

Liu

et al. 2015

Animal

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This study was conducted to investigate the effects of rumen-protected γ-aminobutyric acid (GABA) on feed intake, growth performance and expression of related genes in growing lambs. A total of 24 lambs weaned at age of 50 days were divided into four block of six based on their BW, six lambs within a block were allocated to three pairs, which were then assigned randomly to three treatments with addition of rumen-protected GABA at levels of 0, 70 or 140 mg/day for 6 weeks. Dry matter intake was recorded weekly in three consecutive days, and BW was recorded every two weeks. At the end of the trial, four lambs from each group were slaughtered, and duodenum and ileum mucosa were obtained for measurement of mRNA abundance of GABA receptor and cholecystokinin receptor. Dry matter intake was higher ( P < 0.01) in the lambs fed 140 mg/day GABA than that in the control or 70 mg GABA-fed lambs. Average daily gain and nutrients digestibility were not different ( P > 0.05) among treatments. Lambs fed 140 mg/day GABA had higher mRNA abundance of GABA-B receptor ( P < 0.01) and lower mRNA abundance of cholecystokinin-2 receptor ( P < 0.01) in duodenum mucosa. Serum CCK content was lower ( P < 0.01) in lambs fed 140 mg/day GABA than that in control. It is indicated that GABA may enhance feed intake by regulating GABA-and cholecystokininrelated genes.

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Central and peripheral action of GABAA and GABAB agonists on small intestine motility in rats

Cited by 35 publications

References 26 publications

The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.

The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.

Effect of baclofen on liquid and solid gastric emptying in rats

Effects of γ-aminobutyric acid on feed intake, growth performance and expression of related genes in growing lambs

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