Opposite role played by GABAA and GABAB receptors in the modulation of peristaltic activity in mouse distal colon.

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Abstract

We investigated the role of GABA on intestinal motility using as model the murine distal colon. Effects induced by GABA receptors recruitment were examined in whole colonic segments and isolated circular muscle preparations to analyze their influence on peristaltic reflex and on spontaneous and neurally-evoked contractions. Using a modified Trendelenburg set-up, rhythmic peristaltic contractions were evoked by gradual distension of the colonic segments. Spontaneous and neurally-evoked mechanical activity of circular muscle strips were recorded in vitro as changes in isometric tension. GABA, at low concentrations (10-50µM), potentiated peristaltic activity and the neural cholinergic contractions, whilst it, at higher concentrations (500µM-1mM), had inhibitory effects. GABA excitatory effects were mimicked by muscimol, GABAA-receptor agonist, and prevented by bicuculline, GABAA-receptor antagonist, which per se reduced peristaltic activity and the cholinergic contractile responses. Inhibitory effects were mimicked by baclofen, GABAB-receptor agonist, and antagonized by phaclofen, GABAB-receptor antagonist and by hexamethonium, neural nicotinic receptor antagonist. Guanethidine was ineffective on GABA effects. Non-cholinergic responses were not affected by GABA agents. All drugs failed to affect the response to carbachol. Lastly, GABAC receptor agonist/antagonist had any effect on colonic motility. In conclusion, GABA in mouse distal colon is a modulator of peristaltic activity via the regulation of acetylcholine release from cholinergic neurons through interaction with GABAA or GABAB receptors. GABAA receptors are recruited at low GABA concentrations, increasing acetylcholine release and propulsive activity. At high GABA concentrations the activation of GABAB receptors overrides GABAA receptor effects, decreasing acetylcholine release and peristaltic activity.
Lingua originaleEnglish
pagine (da-a)93-99
Numero di pagine7
RivistaEuropean Journal of Pharmacology
Volume731
Stato di pubblicazionePublished - 2014

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GABA-A Receptors
gamma-Aminobutyric Acid
GABA Agents
Colon
Acetylcholine
Cholinergic Agents
Nicotinic Antagonists
GABA-B Receptors
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Guanethidine
Muscles
Hexamethonium
Cholinergic Neurons
Gastrointestinal Motility
GABA Receptors
Bicuculline
Nicotinic Receptors
Carbachol
Sensory Receptor Cells

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Pharmacology

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title = "Opposite role played by GABAA and GABAB receptors in the modulation of peristaltic activity in mouse distal colon.",
abstract = "We investigated the role of GABA on intestinal motility using as model the murine distal colon. Effects induced by GABA receptors recruitment were examined in whole colonic segments and isolated circular muscle preparations to analyze their influence on peristaltic reflex and on spontaneous and neurally-evoked contractions. Using a modified Trendelenburg set-up, rhythmic peristaltic contractions were evoked by gradual distension of the colonic segments. Spontaneous and neurally-evoked mechanical activity of circular muscle strips were recorded in vitro as changes in isometric tension. GABA, at low concentrations (10-50µM), potentiated peristaltic activity and the neural cholinergic contractions, whilst it, at higher concentrations (500µM-1mM), had inhibitory effects. GABA excitatory effects were mimicked by muscimol, GABAA-receptor agonist, and prevented by bicuculline, GABAA-receptor antagonist, which per se reduced peristaltic activity and the cholinergic contractile responses. Inhibitory effects were mimicked by baclofen, GABAB-receptor agonist, and antagonized by phaclofen, GABAB-receptor antagonist and by hexamethonium, neural nicotinic receptor antagonist. Guanethidine was ineffective on GABA effects. Non-cholinergic responses were not affected by GABA agents. All drugs failed to affect the response to carbachol. Lastly, GABAC receptor agonist/antagonist had any effect on colonic motility. In conclusion, GABA in mouse distal colon is a modulator of peristaltic activity via the regulation of acetylcholine release from cholinergic neurons through interaction with GABAA or GABAB receptors. GABAA receptors are recruited at low GABA concentrations, increasing acetylcholine release and propulsive activity. At high GABA concentrations the activation of GABAB receptors overrides GABAA receptor effects, decreasing acetylcholine release and peristaltic activity.",
keywords = "Cholinergic contraction, Distal colon, GABAA receptors, GABAB receptors, Mouse, Peristaltic activity",
author = "Zizzo, {Maria Grazia} and Mariangela Mastropaolo and Serio, {Rosa Maria} and Michelangelo Auteri",
year = "2014",
language = "English",
volume = "731",
pages = "93--99",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

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TY - JOUR

T1 - Opposite role played by GABAA and GABAB receptors in the modulation of peristaltic activity in mouse distal colon.

AU - Zizzo, Maria Grazia

AU - Mastropaolo, Mariangela

AU - Serio, Rosa Maria

AU - Auteri, Michelangelo

PY - 2014

Y1 - 2014

N2 - We investigated the role of GABA on intestinal motility using as model the murine distal colon. Effects induced by GABA receptors recruitment were examined in whole colonic segments and isolated circular muscle preparations to analyze their influence on peristaltic reflex and on spontaneous and neurally-evoked contractions. Using a modified Trendelenburg set-up, rhythmic peristaltic contractions were evoked by gradual distension of the colonic segments. Spontaneous and neurally-evoked mechanical activity of circular muscle strips were recorded in vitro as changes in isometric tension. GABA, at low concentrations (10-50µM), potentiated peristaltic activity and the neural cholinergic contractions, whilst it, at higher concentrations (500µM-1mM), had inhibitory effects. GABA excitatory effects were mimicked by muscimol, GABAA-receptor agonist, and prevented by bicuculline, GABAA-receptor antagonist, which per se reduced peristaltic activity and the cholinergic contractile responses. Inhibitory effects were mimicked by baclofen, GABAB-receptor agonist, and antagonized by phaclofen, GABAB-receptor antagonist and by hexamethonium, neural nicotinic receptor antagonist. Guanethidine was ineffective on GABA effects. Non-cholinergic responses were not affected by GABA agents. All drugs failed to affect the response to carbachol. Lastly, GABAC receptor agonist/antagonist had any effect on colonic motility. In conclusion, GABA in mouse distal colon is a modulator of peristaltic activity via the regulation of acetylcholine release from cholinergic neurons through interaction with GABAA or GABAB receptors. GABAA receptors are recruited at low GABA concentrations, increasing acetylcholine release and propulsive activity. At high GABA concentrations the activation of GABAB receptors overrides GABAA receptor effects, decreasing acetylcholine release and peristaltic activity.

AB - We investigated the role of GABA on intestinal motility using as model the murine distal colon. Effects induced by GABA receptors recruitment were examined in whole colonic segments and isolated circular muscle preparations to analyze their influence on peristaltic reflex and on spontaneous and neurally-evoked contractions. Using a modified Trendelenburg set-up, rhythmic peristaltic contractions were evoked by gradual distension of the colonic segments. Spontaneous and neurally-evoked mechanical activity of circular muscle strips were recorded in vitro as changes in isometric tension. GABA, at low concentrations (10-50µM), potentiated peristaltic activity and the neural cholinergic contractions, whilst it, at higher concentrations (500µM-1mM), had inhibitory effects. GABA excitatory effects were mimicked by muscimol, GABAA-receptor agonist, and prevented by bicuculline, GABAA-receptor antagonist, which per se reduced peristaltic activity and the cholinergic contractile responses. Inhibitory effects were mimicked by baclofen, GABAB-receptor agonist, and antagonized by phaclofen, GABAB-receptor antagonist and by hexamethonium, neural nicotinic receptor antagonist. Guanethidine was ineffective on GABA effects. Non-cholinergic responses were not affected by GABA agents. All drugs failed to affect the response to carbachol. Lastly, GABAC receptor agonist/antagonist had any effect on colonic motility. In conclusion, GABA in mouse distal colon is a modulator of peristaltic activity via the regulation of acetylcholine release from cholinergic neurons through interaction with GABAA or GABAB receptors. GABAA receptors are recruited at low GABA concentrations, increasing acetylcholine release and propulsive activity. At high GABA concentrations the activation of GABAB receptors overrides GABAA receptor effects, decreasing acetylcholine release and peristaltic activity.

KW - Cholinergic contraction

KW - Distal colon

KW - GABAA receptors

KW - GABAB receptors

KW - Mouse

KW - Peristaltic activity

UR - http://hdl.handle.net/10447/96942

M3 - Article

VL - 731

SP - 93

EP - 99

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -