Functional GABA(A) receptors on rat vagal afferent neurones

Abstract

1. In the present study, in vitro electrophysiology and receptor autoradiography were used to determine whether rat vagal afferent neurones possess γ-aminobutyric acid (GABA)(A) receptors. 2. GABA (1-100 uM) and isoguvacine (3-100 μM) 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 μM) and bicuculline (3 μM) 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 μM) was unable to elicit a depolarization of the rat isolated nodose ganglion preparation at either room temperature or at 36°C, whilst 5-aminovaleric acid (10 uM), a GABA(B) receptor antagonist, was unable to antagonize significantly the GABA-induced depolarization at either room temperature or at 36°C. 4. [3H]-SR95531 (7.2 nM), a GABA(A) 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 GABA(A) binding site density in the medial NTS from 93 ± 7 to 68 ± 6 d.p.m./mm2. This procedure also caused a reduction in GABA(A) 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 GABA(A) receptors located on the soma and central terminals of rat vagal afferent neurones. Additionally, a population of GABA(A) 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.