Dopamine D2 receptors in the rat brain: autoradiographic visualization using a high-affinity selective agonist ligand (original) (raw)
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Dopamine receptors in human brain: Autoradiographic distribution of D2 sites
Neuroscience, 1989
The distribution and density of dopamine D 1 and D 2 receptors were examined by autoradiography in postmortem brain tissue from patients with pathological diagnosis of Parkinson's disease, status lacunaris, clinical parkinsonism without neuropathological lesions and in age-matched controls. The D 1 antagonist [3H]SCH 23390 and the D 2 agonist [3H]CV 205-502 were used as ligands. No significant differences in the distribution or density of D 1 or D 2 receptors were found in Parkinson's disease in the areas examined, including the nucleus caudatus, putamen, globus pallidus and substantia nigra. In contrast, cases presenting lacunar lesions in the striatum showed marked decreases in D 1 and D 2 receptor densities in this region. Patients clinically diagnosed as parkinsonians but without Parkinson's disease lesions or striatal lacunar softenings showed reduced densities of D 2 receptors in the nucleus caudatus and putamen, while in the substantia nigra the densities were comparable to controls. In the basal ganglia of these cases D 1 receptors were slightly decreased.
Journal of Neural Transmission, 1990
Dopamine D 1 and D 2 receptor distributions were studied in the brain of the mouse, rat, guinea pig, cat and monkey by means of in vitro quantitative autoradiography using [3H]SCH 23390 and [3H]CV 205-502 to label D 1 and D 2 subtypes respectively. The distribution of both subtypes of receptors was similar within the basal ganglia of all species investigated. The highest densities for both subtypes were found in the nucleus caudatus, putamen, nucleus accumbens, olfactory tubercle and substantia nigra. Outside of the basal ganglia, differences in the distribution of both receptors were found among the species examined in regions such as cerebellum, cortex, hippocampus, superior colliculus and olfactory bulb. In all species D 1 receptor densities were higher than those of D 2. The absolute amount of both subtypes, however, varied among species. These results indicate that dopamine receptor distribution is well preserved in the basal ganglia during evolution, although differences among species exist in their distribution outside the basal ganglia and their absolute amount.
Dopamine D1 receptor in rat brain: a quantitative autoradiographic study with125I-SCH 23982
Brain Research, 1987
We report the regional distribution and characteristics of 125I-SCH 23982 binding to D~ receptors in rat brain using a quantitative autoradiographic technique. The substantia nigra pars reticulata, the caudate putamen, the nucleus accumbens and the olfactory tubercle had a single class of high affinity binding sites for t25I-SCH 23982. Binding sites were also present in a discrete, continuous band connecting the caudate putamen with the substantia nigra.
Autoradiographic Localization of the Putative D4 Dopamine Receptor in Rat Brain
Neurochem Res, 1997
The putative dopamine D4 receptor protein in rat brain was labelled and quantified autoradiographically using two selective benzamides: [ 3 H]YM-09151-2 which labels D2, D3 and D4 dopamine receptors and [ 3 H]Raclopride which labels D2 and D3. The difference in densities of both ligands at saturable concentrations, show a regional distribution for the putative D4 receptor in the following rank order: hippocampus > caudate putamen > olfactory tubercle = substancia nigra > nucleus accumbens core > cerebral cortex > cerebellum. A calculated value of 0.34 pmol/mg protein was attributable to D4 receptor maximum capacity in caudate putamen and was obtained after subtracting the Bmax of the ligands. Our results show that the distribution of D4 receptor only partially overlaps with the D4 mRNA localization reported earlier and is not only associated to limbic structures but to motor areas as well.
Dopamine receptors in human brain: Autoradiographic distribution of D1 sites
Neuroscience, 1989
The distribution and density of dopamine D 1 and D 2 receptors were examined by autoradiography in postmortem brain tissue from patients with pathological diagnosis of Parkinson's disease, status lacunaris, clinical parkinsonism without neuropathological lesions and in age-matched controls. The D 1 antagonist [3H]SCH 23390 and the D 2 agonist [3H]CV 205-502 were used as ligands. No significant differences in the distribution or density of D 1 or D 2 receptors were found in Parkinson's disease in the areas examined, including the nucleus caudatus, putamen, globus pallidus and substantia nigra. In contrast, cases presenting lacunar lesions in the striatum showed marked decreases in D 1 and D 2 receptor densities in this region. Patients clinically diagnosed as parkinsonians but without Parkinson's disease lesions or striatal lacunar softenings showed reduced densities of D 2 receptors in the nucleus caudatus and putamen, while in the substantia nigra the densities were comparable to controls. In the basal ganglia of these cases D 1 receptors were slightly decreased.
Autoradiographic evidence for the occlusion of rat brain dopamine D3 receptors in vivo
European Journal of Pharmacology, 1992
125I]Iodosulpride binding was studied in frontal rat brain sections by quantitative autoradiography. Using preincubated (= washed) sections, selective labelling and identification of dopamine D 3 receptors was obtained using 0.2 nM [125I]iodosulpride in the presence of 100 nM domperidone for the occlusion of the D 2 receptors. A high density of D 3 receptors was noticed in the islands of Calleja. When preincubation of the sections was omitted, no D 3 receptor labelling could be achieved, indicating tight binding to the receptor of an endogenous inhibitor. Such a tight receptor occupancy was not observed for the D e receptor and various other neurotransmitter receptors. The occlusion of the D 3 receptor could be prevented by tetrabenazine-induced monoamine depletion of the rats. It can be concluded, therefore, that D 3 receptors are massively occupied by a monoamine, likely to be dopamine. This observation prompts the question to what extent dopamine D 3 receptors can become occupied in vivo by systematically applied exogenous compounds.
Neuroscience Letters, 1988
h(l Itolds Dopanllnc receptor Dorsal hlppocampus SK[ 8_5_6 Neurolcptlc Mesohmbocortlcal s\,,tom Aden'date cvdase The mesohmbocortlcal dopamlne (DA) s)stem innervates several brain regmns including the hlppocampus The aim ol the present stud:~ was both to identify and to pharmacologlcalb~ characterize the [)A, receptors located m this brain area The results show that different agomsts Ior Di DA. receptors ,,udl as D~ ltsell SKI ~ 82526 and ( )-apomorphmc were able to increase adenylate cvclase actl~lt,, and Ihcs~ effects ~cre antagomzcd b', halopendol and S( H 23390 Moreover bromocnptmc hsunde and RU 2421 which arc agonlqs lor D DA receptors lnhlbHed the cvchc AMP generating ,,,,stem and these effects ~erc pre,,cnkd bx ( )-sulplrlde According to the paradigm that D~ DA receptors are hnked '.allh aden'date c,~cl,ts~, m a qu~.qulator'r ,aa) while De DA receptors are hnked v~lth the same enz'~mc m an mhlblto~x ~a~ out result,, indicate the presence of both Dt and D2 receptors in rat hlppocampus koc,lhzallon stud-It.,, shov'~ thai both DA receptor subt,/pes are restricted to the dorsal part ol the hlppocampus
European Journal of Pharmacology: Molecular Pharmacology, 1993
The characteristics of dopamine (DA) D 2 receptors were studied in rat hippocampus and for comparison in striatum using the [3H]spiperone radioreceptor assay in vitro. D 2 receptors exhibit a bimodal distribution along the length of the hippocampus. Heterogeneity also exists in the transverse axis with high densities in the molecular layers of the subiculum and CA1 plus CA2. As in the striatum, D 2 receptors in both dorsal and ventral hippocampus display high and low affinity states for agonists, but all three regions differ with regard to the percentage of receptors in these states. The modulation of these affinity states by GTP, Mg 2รท and the iron-chelator, 1,1-O-phenanthroline, differs markedly between dorsal and ventral hippocampus, and between these regions and the striatum. A new model for the modulation of the affinity of D 2 receptors for agonists is presented. These data suggest the presence of regional differences in the composition of the D 2 receptor-regulatory protein complex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994
Potential cellular substrates for functions ascribed to the dopamine D2 receptor were examined in rat brain using immunoperoxidase for localization of a D2 receptor peptide and immunogold staining for the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH). Specificity of the rat polyclonal antiserum, raised against a 15 amino acid fragment from the third intracellular loop of the D2 receptor, was shown by immunoblot analysis and by selective labeling of cultured Chinese hamster ovary cells permanently transfected with the cDNA for the D2 receptor. Although the light microscopic distribution of immunolabeling for the D2 peptide was diffuse, it was selectively localized to regions containing dopamine cells (substantia nigra and ventral tegmental area) or their forebrain projections (dorsal and ventral striatum, nucleus accumbens, and olfactory tubercles). Electron microscopic examination of the medial substantia nigra and ventral tegmental area revealed readily detectable per...
Pnas, 1994
We characterized the binding of [125I~epidepride to dopamine D2-like and D3-like receptors in tissue sections of human striatum. The competition for binding of [125I]epidepride by domperidone, quinpirole, and 7-hydroxy-N,N-di(l-propyl)-2-aminotetralin (7-OH-DPAT) was best fit by assuming one site in the caudate but two sites in nucleus accumbens. Guanosine 5'-[3,v-imidoltriphosphate showed a large modulatory influence in agonist inhibition of [12(I]epidepride binding in caudate but not in nucleus accumbens. The binding of [125I~epidepride in the presence of 7-OH-DPAT (1000-fold selective for D3-like versus D2-like sites) and domperidone (20-fold selective for D2-like versus D3-like sites) was used to quantify the numbers of D2-like and D3-like receptors in areas of human brain. The distribution of D2-like and D3-like receptors was largely nonoverlapping. Binding of [125I~epidepride to D3-like receptors was negligible in the dorsal striatum but was concentrated in islands of dense binding in the nucleus accumbens and ventral putamen that aligned with acetylcholinesterase-poor striosomes. Binding to D3-like receptors was also enriched in the internal globus pallidus, ventral pallidum, septum, islands of Calleja, nucleus basalis, amygdalostriatal transition nucleus of the amygdala, central nucleus of the amygdala, and ventral tegmental area. Binding of [12I5epidepride to D2 but not D3 receptors was detected in cortex and hippocampus. There are two superfamilies of dopamine receptors, designated Dj-like and D2-like (1). This nomenclature is based on their structural and amino acid similarities, as well as their binding profiles. The D2-like family contains D2, D3, and D4 subtypes, which differ with respect to their distribution in rat brain (2-4). Much interest has been focused on the D3 receptor because of its high association with "limbic" components of the rat brain (e.g., ventral striatum) and high affinity for dopamine (2, 5). In fact, it has been proposed that the D3 receptor is the "limbic" dopamine receptor through which antipsychotics could act to modify psychosis (5). However, extension of this hypothesis to the human is