Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: role of GABAA and GABAC receptors

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Abstract

We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) receptor agonist, induced an inhibitory effect, consisting in the reduction of the amplitude of the spontaneous contractions and muscular relaxation, which was antagonised by TPMPA, GABA(C)-receptor antagonist, TTX or N(omega)-nitro-l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not affected by hexamethonium. In conclusion, our study indicates that GABA is a modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA may act through neuronal presynaptic receptors, namely GABA(A) receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABA(C) receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.
Lingua originaleEnglish
pagine (da-a)1685-1690
Numero di pagine6
RivistaNeuropharmacology
Volume52(8)
Stato di pubblicazionePublished - 2007

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GABA Modulators
GABA Receptors
GABA-A Receptors
Duodenum
Muscles
gamma-Aminobutyric Acid
Hexamethonium
Bicuculline
Tetrodotoxin
Presynaptic Receptors
Muscimol
Cholinergic Neurons
GABA-C receptor
NG-Nitroarginine Methyl Ester
Muscle Contraction
Atropine
Nitric Oxide Synthase
Smooth Muscle
Nitric Oxide
Neurons

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

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title = "Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: role of GABAA and GABAC receptors",
abstract = "We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) receptor agonist, induced an inhibitory effect, consisting in the reduction of the amplitude of the spontaneous contractions and muscular relaxation, which was antagonised by TPMPA, GABA(C)-receptor antagonist, TTX or N(omega)-nitro-l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not affected by hexamethonium. In conclusion, our study indicates that GABA is a modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA may act through neuronal presynaptic receptors, namely GABA(A) receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABA(C) receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.",
author = "Flavia Mule' and Zizzo, {Maria Grazia} and Serio, {Rosa Maria}",
year = "2007",
language = "English",
volume = "52(8)",
pages = "1685--1690",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",

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TY - JOUR

T1 - Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: role of GABAA and GABAC receptors

AU - Mule', Flavia

AU - Zizzo, Maria Grazia

AU - Serio, Rosa Maria

PY - 2007

Y1 - 2007

N2 - We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) receptor agonist, induced an inhibitory effect, consisting in the reduction of the amplitude of the spontaneous contractions and muscular relaxation, which was antagonised by TPMPA, GABA(C)-receptor antagonist, TTX or N(omega)-nitro-l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not affected by hexamethonium. In conclusion, our study indicates that GABA is a modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA may act through neuronal presynaptic receptors, namely GABA(A) receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABA(C) receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.

AB - We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) receptor agonist, induced an inhibitory effect, consisting in the reduction of the amplitude of the spontaneous contractions and muscular relaxation, which was antagonised by TPMPA, GABA(C)-receptor antagonist, TTX or N(omega)-nitro-l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not affected by hexamethonium. In conclusion, our study indicates that GABA is a modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA may act through neuronal presynaptic receptors, namely GABA(A) receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABA(C) receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.

UR - http://hdl.handle.net/10447/19573

M3 - Article

VL - 52(8)

SP - 1685

EP - 1690

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -