Functional dopamine D₂ 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 dopamine D2 receptors. 2 Dopamine (10-300IM) 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 M), clozapine (10I1M) or a mixture of raclopride and clozapine (1O gM 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 jAM 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 (1O iM, 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 ['25I]-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.

Blockade of Spinal Dopamine D2 Receptors Enhances the Pressor Effect of Intravenous Quinpirole in Normotensive, Conscious Rats

“…It is unlikely that the quinpirole-induced pressor effect is partly mediated by dopamine D 3 receptor activation. This conclusion is supported by the fact that the nucleus tractus solitarius, which has been suggested as the central site of action of quinpirole on blood pressure (Yang et al 1990), contains a high density of dopamine D 2 , but not D 3 receptors (Gehlert 1993;Lawrence et al 1995). Furthermore, the pressor response of quinpirole has been shown to be significantly reduced in spontaneously hypertensive rats infused intracisternally with an antisense oligonucleotide against dopamine D 2 receptors, but not against D 3 receptors (Van den Buuse 1997).…”

Receptor Crosstalk: Characterization of Mice Deficient in Dopamine D1 and Adenosine A2A Receptors

“…]-NCQ 298) with this procedure and the methodology for D 2 -dopamine receptor autoradiography described elsewhere (Lawrence et al, 1995). Binding remaining in the presence of raclopride (10 mM) was defined as nonspecific.…”

The Metabotropic Glutamate 5 Receptor Antagonist 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine Reduces Ethanol Self-Administration in Multiple Strains of Alcohol-Preferring Rats and Regulates Olfactory Glutamatergic Systems

“…125 I]NCQ298 was purified from the iodination reaction mixture by paper chromatography as previously described (Lawrence et al, 1995). Sections were preincubated in buffer (170 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, 2 mM CaCl 2 , 1 mM MgCl 2 , and 0.001% w/v ascorbic acid) for 30 min.…”