Functional dopamine D2 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 dopamine D2 receptors. 2. Dopamine (10-300 microM) elicited a temperature- and concentration-dependent depolarization of the rat isolated nodose ganglion preparation. When applied to the tissue 15 min prior to agonist, raclopride (10 microM), clozapine (10 microM) or a mixture of raclopride and clozapine (10 microM each) all produced a threefold parallel shift to the right of the dopamine concentration-response curve. In contrast, SCH 23390 (100 nM), phentolamine and propranolol (1 microM each) failed to antagonize the dopamine-mediated depolarization. 3. [125I]-NCQ 298 (0.5 nM), a D2 selective radioligand, bound topographically to sections of rat brainstem. Densitometric quantification of autoradiograms revealed 93.8 +/- 0.5% specific binding of this salicylamide radioligand, as determined by raclopride (10 microM, n = 10 animals). Binding was highest in the nucleus tractus solitarius (NTS), particularly 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 the contralateral NTS. Furthermore, the loss of binding was confined to the dorsal aspect of the medial subnucleus of the NTS. Sham surgery had no effect on the binding of [125I]-NCQ 298 in rat brainstem. 5. The present data provide evidence for the presence of functionally relevant dopamine D2 receptors on both the soma and central terminals of rat vagal afferent neurones. In addition, the majority of D2 receptors in the rat NTS appear to be located postsynaptically with respect to vagal terminals, and are presumably located either on ascending glossopharyngeal terminals, descending terminals from higher brain regions or on neuronal cell bodies within the NTS.
Lawrence
A J
AJ
Department of Pharmacology, Monash University, Clayton, Vic., Australia.
Krstew
E
E
Jarrott
B
B
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001345:Autoradiography; D001933:Brain Stem / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008297:Male; D009620:Nodose Ganglion / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012457:Salicylamides / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects*
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D004298:Dopamine; C064246:NCQ 298