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           Search results for: Dopamine D2 Receptor , Antigen blocking peptide    

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#24184556   2013/11/18 Save this To Up

Brain human monoclonal autoantibody from sydenham chorea targets dopaminergic neurons in transgenic mice and signals dopamine D2 receptor: implications in human disease.

How autoantibodies target the brain and lead to disease in disorders such as Sydenham chorea (SC) is not known. SC is characterized by autoantibodies against the brain and is the main neurologic manifestation of streptococcal-induced rheumatic fever. Previously, our novel SC-derived mAb 24.3.1 was found to recognize streptococcal and brain Ags. To investigate in vivo targets of human mAb 24.3.1, VH/VL genes were expressed in B cells of transgenic (Tg) mice as functional chimeric human VH 24.3.1-mouse C-region IgG1(a) autoantibody. Chimeric human-mouse IgG1(a) autoantibody colocalized with tyrosine hydroxylase in the basal ganglia within dopaminergic neurons in vivo in VH 24.3.1 Tg mice. Both human mAb 24.3.1 and IgG1(a) in Tg sera were found to react with human dopamine D2 receptor (D2R). Reactivity of chorea-derived mAb 24.3.1 or SC IgG with D2R was confirmed by dose-dependent inhibitory signaling of D2R as a potential consequence of targeting dopaminergic neurons, reaction with surface-exposed FLAG epitope-tagged D2R, and blocking of Ab reactivity by an extracellular D2R peptide. IgG from SC and a related subset of streptococcal-associated behavioral disorders called "pediatric autoimmune neuropsychiatric disorder associated with streptococci" (PANDAS) with small choreiform movements reacted in ELISA with D2R. Reaction with FLAG-tagged D2R distinguished SC from PANDAS, whereas sera from both SC and PANDAS induced inhibitory signaling of D2R on transfected cells comparably to dopamine. In this study, we define a mechanism by which the brain may be altered by Ab in movement and behavioral disorders.

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Beta Amyloid (42) ELISA K Beta Amyloid (1 40) ELISA Beta Amyloid (40) ELISA K Beta Amyloid (1 40) ELISA Anti AGO2 Human, Monoclon Anti AGO2 Human, Monoclon Interferon-a Receptor Typ Mouse Anti-Human Interleu interleukin 17 receptor C interferon-alpha receptor Anti 3 DG imidazolone Mon Human integrin aVb3, affi

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#19940170   2009/11/26 Save this To Up

Neural cell adhesion molecule modulates dopaminergic signaling and behavior by regulating dopamine D2 receptor internalization.

The dopaminergic system plays an important role in the etiology of schizophrenia, and most antipsychotic drugs exert their functions by blocking dopamine D(2) receptors (D(2)Rs). Since the signaling strength mediated by D(2)Rs is regulated by internalization and degradation processes, it is crucial to identify molecules that modulate D(2)R localization at the cell surface. Here, we show that the neural cell adhesion molecule (NCAM) promotes D(2)R internalization/desensitization and subsequent degradation via direct interaction with a short peptide in the third intracellular loop of the D(2)R. NCAM deficiency in mice leads to increased numbers of D(2)Rs at the cell surface and augmented D(2)R signaling as a result of impaired D(2)R internalization. Furthermore, NCAM-deficient mice show higher sensitivity to the psychostimulant apomorphine and exaggerated activity of dopamine-related locomotor behavior. These results demonstrate that, in addition to its classical function in cell adhesion, NCAM is involved in regulating the trafficking of the neurotransmitter receptor D(2)R as well as receptor-mediated signaling and behavior, thus implicating NCAM as modulator of the dopaminergic system and a potential pharmacological target for dopamine-related neurological and psychiatric disorders.

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T-Cell Receptor Signaling Human T Cell Receptor Sig Human vascular cell adhes Human soluble vascular ce Rabbit Anti-Dopamine D2 R Rabbit Anti-Dopamine D2 R Rabbit Anti-Dopamine D2 R Rabbit Anti-Dopamine D2 R Androgen Receptor (Phosph Androgen Receptor (Phosph Rabbit Anti-Human Androge Rabbit Anti-Human Androge

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#9749715   1998/10/22 Save this To Up

Development and characterization of antibodies directed against the mouse D4 dopamine receptor.

Polyclonal antibodies against the mouse D4 dopamine receptor have been developed in order to investigate the anatomical localization of this receptor in the mouse brain. Two antibodies were generated against specific peptides corresponding to predicted extracellular and intracellular regions of the D4 protein. Specificity of these antibodies was demonstrated on human embryonic kidney 293 (HEK 293) cells transfected with different dopamine receptor subtypes; immunoreactivity was detected only in cells transfected with the mouse D4 dopamine receptor cDNA. Following in vitro transcription/translation of the mouse D4 cDNA, a single protein band of 36 kDa was selectively immunoprecipitated with the anti-D4 antibodies. The antibodies also detected a single protein of 36 kDa in Western blot of HEK 293 cells transiently transfected with the mouse D4 receptor. These antibodies were able to detect the D4 receptor in several regions of the mouse brain. In the regions examined, D4 immunoreactivity was found in neurones located in layers II-VI of the frontal and piriform cortices, with the highest concentration in layer II; in scattered neurones in the caudate putamen and in larger neurones in the globus pallidus. In all experiments, both antibodies exhibit the same specificity, and all immunoreactivity could be abolished by preincubation with the corresponding peptide antigen.

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Goat Anti- Dopamine recep Rabbit Anti-Dopamine D4 R Dopamine antibody, Monocl Mouse Anti-Dopamine Antib Mouse Anti-Human Glucocor Mouse Anti-Human Glucocor Mouse Anti-Growth Hormone Mouse Anti-Human Ryanodin Mouse Anti-Human TNF Rece Mouse Anti-Human AFP Rece Mouse Anti-Human G-CSF Re Rat Anti-Mouse beta-Gluca

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