FUNCTIONAL DOPAMINE D-2 RECEPTORS ON RAT VAGAL AFFERENT NEURONS

Citation
Aj. Lawrence et al., FUNCTIONAL DOPAMINE D-2 RECEPTORS ON RAT VAGAL AFFERENT NEURONS, British Journal of Pharmacology, 114(7), 1995, pp. 1329-1334
Citations number
44
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00071188
Volume
114
Issue
7
Year of publication
1995
Pages
1329 - 1334
Database
ISI
SICI code
0007-1188(1995)114:7<1329:FDDROR>2.0.ZU;2-B
Abstract
1 In the present study in vitro electrophysiology and receptor autorad iography were used to determine whether rat vagal afferent neurones po ssess dopamine D-2 receptors. 2 Dopamine (10-300 mu M) elicited a temp erature- and concentration-dependent depolarization of the rat isolate d nodose ganglion preparation. When applied to the tissue 15 min prior to agonist, raclopride (10 mu M), clozapine (10 mu M) or a mixture of raclopride and clozapine (10 mu M each) all produced a threefold para llel shift to the right of the dopamine concentration-response curve. In contrast, SCH 23390 (100 nM), phentolamine and propranolol (1 mu M each) failed to antagonize the dopamine-mediated depolarization. 3 [I- 125]-NCQ 298 (0.5 nM), a D-2 selective radioligand, bound topographica lly to sections of rat brainstem. Densitometric quantification of auto radiograms revealed 93.8 +/- 0.5% specific binding of this salicylamid e radioligand, as determined by raclopride (10 mu M, n = 10 animals). Binding was highest in the nucleus tractus solitarius (NTS), particula rly the medial and gelatinous subnuclei. In addition, specific binding was also observed in the interpolar spinal trigeminal nucleus and the inferior olive. 4 Unilateral nodose ganglionectomy caused a 36.6 +/- 3.0% reduction in specific binding in the denervated NTS compared to t he contralateral NTS. Furthermore, the loss of binding was confined to the dorsal aspect of the medial subnucleus of the NTS. Sham surgery h ad no effect on the binding of [I-125]-NCQ 298 in rat brainstem. 5 The present data provide evidence for the presence of functionally releva nt dopamine D-2 receptors on both the soma and central terminals of ra t vagal afferent neurones. In addition, the majority of D-2 receptors in the rat NTS appear to be located postsynaptically with respect to v agal terminals, and are presumably located either on ascending glossop haryngeal terminals, descending terminals from higher brain regions or on neuronal cell bodies within the NTS.