Disease relevance of Drd2

• Dopamine receptor 2 (Dp-r2) agonists, used in the treatment of human hyperprolactinemia including pregnancy, inhibit VEGFR-2-dependent VP and angiogenesis when administered at high doses in animal cancer models [1].
• The dopamine D2 receptor, which attenuates acetylcholine release, has been implicated in drug relapse and is targeted by therapeutic drugs that are used to treat a variety of neurological disorders including Tourette Syndrome, Parkinson's disease and schizophrenia [2].
• In the earlier studies, the dopamine D2 receptor agonist bromocriptine (BC) and somatostatin analog octreotide (OCT) were found to inhibit the growth of the estrogen-induced rat prolactinoma [3].
• CONCLUSIONS: These results suggest that in anaesthetised and conscious normotensive rats, the bromocriptine induced tachycardia is not related to a release of adrenaline from the adrenal medulla but could be elicited by central dopamine D-2 receptor stimulation through a possible increase in cardiac sympathetic tone [4].
• The neurokinin1 receptor antagonist CP-99,994 reduces catalepsy produced by the dopamine D2 receptor antagonist raclopride: correlation with extracellular acetylcholine levels in striatum [5].

Psychiatry related information on Drd2

• Biphasic effects of dopamine D-2 receptor agonists on sleep and wakefulness in the rat [6].
• Bilateral injection of haloperidol (5 micrograms/side) or the selective dopamine D2 receptor antagonist, (+/-)-sulpiride (200 ng/side) before the hippocampal AD, into the NAC selectively reduced rearings and locomotor activity, but not the number of wet-dog shakes and face washes [7].
• Dopamine D2 receptor gene expression in rat lines selected for differences in voluntary alcohol consumption [8].
• Nicotine, by activating the nicotinic acetylcholine receptors, attenuated the impairment of short-term memory induced by muscarinic or dopamine D2 receptor blockade [9].
• REM sleep deprivation alters dopamine D2 receptor binding in the rat frontal cortex [10].

High impact information on Drd2

• Membranes from transfected cells showed high-affinity binding of the serotonin antagonists spiperone, ketanserin and mianserin, low affinity for haloperidol (a dopamine D2 receptor antagonist), 8-OH-DPAT as well as MDL-72222 and no detectable binding of [3H]serotonin [11].
• Dual probe in vivo microdialysis was used to investigate gamma-aminobutyric acid (GABA) release in the substantia nigra and the globus pallidus, which represent the terminal sites of the dopamine D1 receptor regulated striatonigral and the dopamine D2 receptor regulated striatopallidal GABA pathways, respectively [12].
• However, we observe a dissociation in the time course of activation of c-fos and proenkephalin mRNA in rat striatum after administration of the dopamine D2 receptor antagonist haloperidol [13].
• Antipsychotic drugs with potent dopamine D2 receptor antagonist properties, such as haloperidol, induced both c-fos and zif268 mRNA in the caudate-putamen; however, the atypical antipsychotic drug clozapine induced zif268 but not c-fos mRNA in that region [14].
• A three-dimensional model of the dopamine D2 receptor, assumed to be a target of antipsychotic drug action, was constructed from its amino acid sequence [15].

Chemical compound and disease context of Drd2

• N-0923, a selective dopamine D2 receptor agonist, is efficacious in rat and monkey models of Parkinson's disease [16].
• Domperidone, a dopamine D2-receptor antagonist, substantially reduced the respiratory depression caused by dopamine, both in capsaicin-treated and in control animals, suggesting that a D2-receptor was involved in the response [17].
• These studies suggest that anti-parkinsonian treatments which are not associated with an elevation in PPE-B and/or normalize elevated PPE-A precursor expression, such as NMDA-receptor antagonists or long-acting dopamine D2 receptor agonists, e.g., cabergoline or ropinirole, may reduce dyskinesia in Parkinson's disease [18].
• However, the cannabinoid receptor antagonist SR 141716A inhibited oleamide-induced analgesia in the tail-flick assay, the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline reversed the analgesia and hypothermia, and the dopamine D2 receptor antagonist L 741626 blocked oleamide's locomotor and analgesic actions [19].
• The dopamine D2 receptor antagonist, domperidone, caused hypertension in ropinirole-but not vehicle-treated rats [20].

Biological context of Drd2

• A 100 mug/kg low-dose Dp-r2 agonist cabergoline reversed VEGFR-2-dependent VP without affecting luteal angiogenesis through partial inhibition of ovarian VEGFR-2 phosphorylation levels [1].
• Dopamine D2 receptor stimulation of mitogen-activated protein kinases mediated by cell type-dependent transactivation of receptor tyrosine kinases [21].
• This site may be a dopamine D2 receptor-linked monoamine oxidase inhibitor-displaceable quinpirole binding site, the enzyme monoamine oxidase-A, or other clorgyline binding sites [22].
• Dopamine D2 receptor mRNA in the pituitary during the oestrous cycle, pregnancy and lactation in the rat [23].
• Gene expression was not affected by more than 1.5-fold at the time points in the striatum, although 65% dopamine depletions occurred, but the plasma membrane-associated dopamine transporter and dopamine D2 receptor were decreased about 40% in the substantia nigra at 64 h and 14 days post-AMPH [24].

Anatomical context of Drd2

• Results in the animal model and the safe clinical profile of Dp-r2 agonists encouraged us to administer cabergoline to oocyte donors at high risk for developing the syndrome [1].
• Dopamine D2 receptor modulation of carotid body type 1 cell intracellular calcium in developing rats [25].
• Molecular, chemical, and anatomical characterization of globus pallidus dopamine D2 receptor mRNA-containing neurons [26].
• On the contrary, a clear reduction in the production of NO was found in neutrophils from rats treated with bromocriptine (BRC) (2 mg/kg s.c.), a dopamine D2-receptor agonist [27].
• Dopamine D2 receptor high-affinity binding is impaired in these tumours, and the rat GH3 cell line behaves in a similar way [28].

Associations of Drd2 with chemical compounds

• Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)-beta1, and TGF-beta type II receptor interact to inhibit the growth of pituitary lactotropes [29].
• Repeated sucrose access influences dopamine D2 receptor density in the striatum [30].
• Dopamine D2 receptor mRNA levels in the anterior pituitary of OVX, E2-treated rats were significantly decreased at 1800 h, compared with those at 1000 h [31].
• Dopamine (1-10 mg/kg) or atropine (3 mg/kg) was administered s.c. twice, 30 min before and 8 hr after indomethacin, while sulpiride (3 mg/kg) and domperidone (3 mg/kg), the dopamine D2 receptor antagonists, or yohimbine (10 mg/kg), the alpha2-adrenoceptor antagonist, were administered s.c. twice, 30 min before each dosing of dopamine [32].
• The atypical neuroleptics remoxipride, clozapine, perlapine, seroquel, and melperone had low affinity for the dopamine D2 receptor (radioligand-independent dissociation constants of 30 to 90 nM) [33].

Physical interactions of Drd2

• A study was done to determine if the Fos and neurotensin immunoreactivities elicited in the rat striatal complex by the selective dopamine D2 receptor antagonist, S(-)-eticlopride hydrochloride are co-localized in the same neurons [34].

Regulatory relationships of Drd2

• Effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on the prolactin suppression induced by a series of full and partial dopamine D2 receptor agonists in male rats [35].
• Furthermore, overexpression of Endo3 in an olfactory epithelium-derived cell line suppressed dopamine D2 receptor-mediated endocytosis and therefore accelerated its dopamine-induced differentiation [36].
• The peptide neurotensin is expressed in both dopamine D1 receptor-bearing neurons of the direct striatonigral pathway and dopamine D2 receptor-bearing neurons of the indirect striatopallidal pathway [37].
• Simultaneous detection of radioactive and non-radioactive probes showed that the majority of adenosine A2A receptor messenger RNA-containing neurons in the dorsal and ventral striatum co-expressed dopamine D2 receptor messenger RNA and preproenkephalin A messenger RNA [38].
• MDMA (5 mg kg(-1) i.p.) produced a rapid decrease in rectal temperature in rats at Ta 15 degrees C. This response was blocked by pretreatment with the dopamine D2 receptor antagonist remoxipride (10 mg kg(-1) i.p.), but unaltered by pretreatment with the D1 antagonist SCH23390 (1.1 mg kg(-1) i.p) [39].

Other interactions of Drd2

• Analysis of dopamine D2 receptor mRNA by in situ hybridization and Northern hybridization detected expression of dopamine receptor in GH3 cells, but the receptor mRNA levels were not modified by EGF or E2 treatment in complete serum or in serum-free media [40].
• The dopamine response was also blocked by 1-sulpiride, a specific dopamine D2 receptor antagonist, and mimicked by RU 24926, a specific dopamine D2 receptor agonist, suggesting that the dopamine effect on BAY-K-8644-stimulated PRL secretion was mediated through a D2 dopamine receptor [41].
• The dopamine D2-receptor agonist quinpirole (10 microM) had little effect on the TRH-induced [Ca2+]i rise in bAP cells, but abolished the increase in FM 1-43 fluorescence [42].
• The blockade of dopamine D2 receptors by the dopamine D2 receptor antagonist, sulpiride, diminished the inhibitory effects of neuropeptide Y on the stimulation-evoked [3H]dopamine release [43].
• A strong dopamine D4 receptor protein immunoreactivity displaying the same localization of dopamine D2 receptor protein was observed in pial and mesenteric arteries, but not in renal artery branches [44].

Analytical, diagnostic and therapeutic context of Drd2

• However, immobilization prevented a decrease in dopamine D2 receptor mRNA levels at 1800 h [31].
• Dopamine D-2 receptor binding was measured with in vitro autoradiography, using [125I]-sulpiride as the ligand [45].
• The in vivo binding of [11C]SCH23390 (dopamine D1 receptor antagonist) and [11C]N-methylspiperone (NMSP; dopamine D2 receptor antagonist) in the striatal region was measured by a high-resolution positron emission tomography at 1 and 3.5 hr, respectively, after the last cocaine or saline injection [46].
• Evaluation of [123I]IBZM pinhole SPECT for the detection of striatal dopamine D2 receptor availability in rats [47].
• We decided to evaluate the temporal relationship of dopamine D2 receptor-mediated drug seeking behavior and behavioral sensitization in animals with a history of cocaine and heroin self-administration [48].

References