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Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects.
Aliment Pharmacol Ther. 2003 Oct 01; 18(7):699-704.AP

Abstract

BACKGROUND

Transient lower oesophageal sphincter relaxation and low lower oesophageal sphincter pressure are the main mechanisms of reflux. It has recently been shown that the stimulation of gamma-aminobutyric acid type B (GABAB) receptors by baclofen decreases the rate of transient lower oesophageal sphincter relaxation and increases the lower oesophageal sphincter pressure in healthy humans. Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors.

AIM

To evaluate the effect of valproic acid on transient lower oesophageal sphincter relaxation, lower oesophageal sphincter pressure and gastro-oesophageal reflux.

METHODS

Thirteen healthy subjects underwent 2-h post-prandial oesophageal motility and pH monitoring on two separate occasions after the oral administration of 1 g valproic acid or placebo.

RESULTS

Valproic acid increased the lower oesophageal sphincter pressure by 41% (14.0 +/- 2.1 mmHg vs. 9.9 +/- 2.0 mmHg after placebo, P<0.02), but did not affect the rate of transient lower oesophageal sphincter relaxation (7.9 +/- 1.0/h vs. 8.2 +/- 0.9/h after placebo), the number of reflux episodes or gastro-oesophageal reflux.

CONCLUSIONS

Non-selective GABA receptor stimulation may be beneficial to reflux patients with low lower oesophageal sphincter pressure, but exerts a different modulation of transient lower oesophageal sphincter relaxation than the selective stimulation of GABAB receptors.

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Authors+Show Affiliations

Cantù P
Cattedra di Gastroenterologia, Dipartimento di Scienze Mediche, University of Milan, IRCCS Ospedale Maggiore, Milan, Italy.
Carmagnola S
No affiliation info available
Savojardo D
No affiliation info available
Allocca M
No affiliation info available
Penagini R
No affiliation info available

MeSH

AdultAgedAged, 80 and overDeglutitionEsophagogastric JunctionFemaleGABA AgentsGastroesophageal RefluxGastrointestinal MotilityHumansHydrogen-Ion ConcentrationMaleManometryMiddle AgedMuscle RelaxationReceptors, GABAValproic Acid

Pub Type(s)

Clinical Trial
Evaluation Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14510743

Citation

Cantù, P, et al. "Effect of Non-selective Gamma-aminobutyric Acid Receptor Stimulation On Motor Function of the Lower Oesophageal Sphincter and Gastro-oesophageal Reflux in Healthy Human Subjects." Alimentary Pharmacology & Therapeutics, vol. 18, no. 7, 2003, pp. 699-704.
Cantù P, Carmagnola S, Savojardo D, et al. Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects. Aliment Pharmacol Ther. 2003;18(7):699-704.
Cantù, P., Carmagnola, S., Savojardo, D., Allocca, M., & Penagini, R. (2003). Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects. Alimentary Pharmacology & Therapeutics, 18(7), 699-704.
Cantù P, et al. Effect of Non-selective Gamma-aminobutyric Acid Receptor Stimulation On Motor Function of the Lower Oesophageal Sphincter and Gastro-oesophageal Reflux in Healthy Human Subjects. Aliment Pharmacol Ther. 2003 Oct 1;18(7):699-704. PubMed PMID: 14510743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects. AU - Cantù,P, AU - Carmagnola,S, AU - Savojardo,D, AU - Allocca,M, AU - Penagini,R, PY - 2003/9/27/pubmed PY - 2004/1/24/medline PY - 2003/9/27/entrez SP - 699 EP - 704 JF - Alimentary pharmacology & therapeutics JO - Aliment Pharmacol Ther VL - 18 IS - 7 N2 - BACKGROUND: Transient lower oesophageal sphincter relaxation and low lower oesophageal sphincter pressure are the main mechanisms of reflux. It has recently been shown that the stimulation of gamma-aminobutyric acid type B (GABAB) receptors by baclofen decreases the rate of transient lower oesophageal sphincter relaxation and increases the lower oesophageal sphincter pressure in healthy humans. Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors. AIM: To evaluate the effect of valproic acid on transient lower oesophageal sphincter relaxation, lower oesophageal sphincter pressure and gastro-oesophageal reflux. METHODS: Thirteen healthy subjects underwent 2-h post-prandial oesophageal motility and pH monitoring on two separate occasions after the oral administration of 1 g valproic acid or placebo. RESULTS: Valproic acid increased the lower oesophageal sphincter pressure by 41% (14.0 +/- 2.1 mmHg vs. 9.9 +/- 2.0 mmHg after placebo, P<0.02), but did not affect the rate of transient lower oesophageal sphincter relaxation (7.9 +/- 1.0/h vs. 8.2 +/- 0.9/h after placebo), the number of reflux episodes or gastro-oesophageal reflux. CONCLUSIONS: Non-selective GABA receptor stimulation may be beneficial to reflux patients with low lower oesophageal sphincter pressure, but exerts a different modulation of transient lower oesophageal sphincter relaxation than the selective stimulation of GABAB receptors. SN - 0269-2813 UR - https://www.unboundmedicine.com/medline/citation/14510743/Effect_of_non_selective_gamma_aminobutyric_acid_receptor_stimulation_on_motor_function_of_the_lower_oesophageal_sphincter_and_gastro_oesophageal_reflux_in_healthy_human_subjects_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0269-2813&amp;date=2003&amp;volume=18&amp;issue=7&amp;spage=699 DB - PRIME DP - Unbound Medicine ER -