Premium
Activation of both phasic and tonic GABAA¬ receptors modulates vagal efferent outflow regulating gastric motor functions
Author(s) -
Reagan Zachary K,
Browning Kirsteen N
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1157.10
Subject(s) - dorsal motor nucleus , gabaa receptor , efferent , chemistry , tonic (physiology) , endocrinology , receptor , medicine , agonist , neuroscience , vagus nerve , biology , stimulation , afferent
The dorsal motor nucleus of the vagus (DMV) provides the parasympathetic innervation to the stomach. DMV neurons display both synaptic and extrasynaptic GABA A receptors that are activated by phasic and tonic GABA release, respectively. Studies have demonstrated that ongoing activation of GABA A receptors is critical in determining vagal efferent outflow to the stomach. The present study was designed to investigate whether phasic and/or tonic GABA A receptors are involved in the regulation of gastric tone. Miniaturized strain gauges were sutured to the ventral surface of the gastric corpus in male Sprague‐Dawley rats (175–300g). The GABA A receptor antagonists, gabazine (0.78–6.25pmol) and/or bicuculline methiodide (BMI; 25–100pmol), were microinjected into the dorsal vagal complex and the increase in gastric tone expressed relative to the maximal increase induced following i.v. application of the non‐selective muscarinic agonist, bethanecol (352pmol; 1ml). At low doses, gabazine acts selectively on extrasynaptic receptors, whereas BMI acts on both synaptic and extrasynaptic receptors. Gabazine increased gastric tone 5.1±1.7% at 0.78pmol, n=10, increasing to 15.3±1.74% and 19.1±5.94% in response to 3.125 and 6.25pmol, n = 5,6, respectively (P<0.05 vs 0.78pmol for each). At lower doses, BMI induced similar increases in gastric tone (11.0±4.7% and 14.9±5.5% at 25 and 50pmol, n = 8,8, respectively) whereas the response was significantly greater at 100pmol (35.7±17.8%, n=4, P<0.05). These data suggest that the activity of DMV neurons, hence vagal efferent outflow to the stomach, is regulated by both synaptic and extrasynaptic GABA A receptors implying a more complex synaptic modulation than previously considered. Supported by NSF IOS 11489364