GABAergic effects on nucleus tractus solitarius neurons receiving gastric vagal inputs.
Single units in the region of the medial nucleus tractus solitarius (NTS), responding to electrical stimulation of gastric vagal fibers, were recorded in an in vitro neonatal rat brainstem-gastric preparation. gamma-Aminobutyric acid (GABA) subreceptor agonists and antagonists were applied to the gastric and brainstem compartments of the bath chamber to evaluate the peripheral gastric and central brainstem GABAergic effects on NTS neuronal activity. The gastric effects of the GABAA receptor agonist muscimol and GABAB receptor agonist baclofen were evaluated on 55 tonic units that received the gastric vagal inputs. For approximately 58% (32 of 55) and 38% (21 of 55) of the units observed, muscimol (30 microM; IC50 = 2.0 microM) and baclofen (30 microM; IC50 = 1.5 microM) in the gastric compartment induced a concentration-dependent inhibition of 36.2 +/- 3.1% (mean +/- S.E.) and 31.0 +/- 2.9% of the control level of the NTS neuronal activity, respectively. The brainstem effects of muscimol and baclofen were tested on 51 units. For approximately 90% (46 of 51) and 78% (40 of 51) of the units tested, muscimol (30 microM; IC50 = 1.3 microM) and baclofen (30 microM; IC50 = 1.1 microM) in the brainstem compartment produced a concentration-dependent inhibition of 54.1 +/- 3.4% and 48.9 +/- 3. 5% of the control level, respectively. The remaining NTS units were not affected by these two GABA agonists. Bicuculline (10 microM) and saclofen (10 microM), the GABAA and GABAB subreceptor antagonists, competitively antagonized the gastric and brainstem effects by muscimol and baclofen, respectively. Our results demonstrated that both GABAA and GABAB receptors in the stomach and brainstem play an important role in activity modulation of the medial NTS neurons receiving gastric vagal inputs in neonatal rats.
Committee on Clinical Pharmacology and the Department of Anesthesia and Critical Care, The Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637, USA. cyuan@midway.uchicago.edu
C S
CS
Yuan
D
D
Liu
A S
AS
Attele
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology*; D013270:Stomach / Q000294:innervation*; D014630:Vagus Nerve / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen