Functional GABAA receptors on rat vagal afferent neurones.
1. In the present study, in vitro electrophysiology and receptor autoradiography were used to determine whether rat vagal afferent neurones possess gamma-aminobutyric acid (GABA)A receptors. 2. GABA (1-100 microM) and isoguvacine (3-100 microM) caused a concentration-dependent depolarization of the rat isolated nodose ganglion preparation at room temperature. When applied to the tissue 20 min before the agonist, SR95531 (3 microM) and bicuculline (3 microM) caused a parallel shift to the right of the GABA and isoguvacine concentration-response curves, yielding shifts of 81 fold and 117 fold for SR95531 and 4 fold and 12 fold for bicuculline, respectively. 3. Baclofen (10 nM-100 microM) was unable to elicit a depolarization of the rat isolated nodose ganglion preparation at either room temperature or at 36 degrees C, whilst 5-aminovaleric acid (10 microM), a GABAB receptor antagonist, was unable to antagonize significantly the GABA-induced depolarization at either room temperature or at 36 degrees C. 4. [3H]-SR95531 (7.2 nM), a GABAA receptor-selective antagonist, bound topographically to sections of rat brainstem. Specific binding was highest in the medial nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve (DMVN). Binding was also observed in certain medullary reticular nuclei, in particular the parvocellular reticular nucleus. 5. Unilateral nodose ganglionectomy caused a reduction in GABAA binding site density in the medial NTS from 93 +/- 7 to 68 +/- 6 d.p.m./mm2. This procedure also caused a reduction in GABAA binding site density in the side of the NTS contralateral to the lesion, from 151 +/- 12 to 93 +/- 7 d.p.m./mm2. Sham surgery had no effect on the binding of [3H]-SR95531 in rat brainstem. 6. The present data provide evidence for the presence of GABAA receptors located on the soma and central terminals of rat vagal afferent neurones. Additionally, a population of GABAA receptors is evidenced postsynaptically in the rat NTS with respect to vagal afferent terminals. These data are discussed in relation to the functional pharmacology of GABA in this region of the NTS.
Ashworth-Preece
M
M
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Krstew
E
E
Jarrott
B
B
Lawrence
A J
AJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001640:Bicuculline / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003714:Denervation; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D007539:Isonicotinic Acids; D011724:Pyridazines; D011963:Receptors, GABA-A; D015763:2-Amino-5-phosphonovalerate; C049853:gabazine; D001640:Bicuculline; C015300:isoguvacine