23 January 1997, Volume 120, Issue 3, Pages 469 – 475

Article

Functional GABAA receptors on rat vagal afferent neurones Mark Ashworth-Preece1, Elena Krstew, Bevyn Jarrott & Andrew J. Lawrence Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3168, Australia     1Author for correspondence

Keywords

-Aminobutyric acid (GABA);   GABAA receptors;   [3H]-SR95531;   nodose ganglion;   vagus nerve;   nucleus tractus solitarius;   in vitro electrophysiology;   autoradiography

Abstract

1   In the present study, in vitro electrophysiology and receptor autoradiography were used to determine whether rat vagal afferent neurones possess -aminobutyric acid (GABA)A receptors. 2   GABA (1 – 100 µM) 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 µM), a GABAB 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 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.

Received 9 July, 96; Revised 27 September, 96; Accepted 15 October, 96

^© Macmillan Publishers Ltd 1997