FUNCTIONAL GABA(A) RECEPTORS ON RAT VAGAL AFFERENT NEURONS

1 In the present study, in vitro electrophysiology and receptor autora diography were used to determine whether rat vagal afferent neurones p ossess gamma-aminobutyric acid (GABA)(A) receptors. 2 GABA (1-100 mu M ) and isoguvacine (3-100 mu M) caused a concentration-dependent depola rization of the rat isolated nodose ganglion preparation at room tempe rature. When applied to the tissue 20 min before the agonist, SR95531 (3 mu M) and bicuculline (3 mu M) caused a parallel shift to the right of the GABA and isoguvacine concentration-response curves, yielding s hifts of 81 fold and 117 fold for SR95531 and 4 fold and 12 fold for b icuculline, respectively. 3 Baclofen (10 nM-100 mu M) was unable to el icit a depolarization of the rat isolated nodose ganglion preparation at either room temperature or at 36 degrees C, whilst 5-aminovaleric a cid (10 mu M), a GABA(B) receptor antagonist, was unable to antagonize significantly the GABA-induced depolarization at either room temperat ure or at 36 degrees C. 4 [H-3]-SR95531 (7.2 nM), a GABA(A) receptor-s elective antagonist, bound topographically to sections of rat brainste m. Specific binding was highest in the medial nucleus tractus solitari us (NTS) and dorsal motor nucleus of the vagus nerve (DMVN). Binding w as also observed in certain medullary reticular nuclei, in particular the parvocellular reticular nucleus. 5 Unilateral nodose ganglionectom y caused a reduction in GABA(A) binding site density in the medial NTS from 93 +/- 7 to 68 +/- 6 d.p.m./mm(2). This procedure also caused a reduction in GABA(A) binding site density in the side of the NTS contr alateral to the lesion, from 151 +/- 12 to 93 +/- 7 d.p.m./mm(2). Sham surgery had no effect on the binding of [H-3]-SR95531 in rat brainste m. 6 The present data provide evidence for the presence of GABA(A) rec eptors located on the soma and central terminals of rat vagal afferent neurones. Additionally, a population of GABA(A) receptors is evidence d postsynaptically in the rat NTS with respect to vagal afferent termi nals. These data are discussed in relation to the functional pharmacol ogy of GABA in this region of the NTS.