A5051549942- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- Computational Drug Discovery Methods
- Neurological disorders and treatments
- Cellular transport and secretion
- Pharmacogenetics and Drug Metabolism
- Pharmacological Receptor Mechanisms and Effects
- S100 Proteins and Annexins
- Nitric Oxide and Endothelin Effects
- Photoreceptor and optogenetics research
- Pharmacological Effects and Assays
- Monoclonal and Polyclonal Antibodies Research
- Medical Imaging Techniques and Applications
- Neural dynamics and brain function
- Immune Response and Inflammation
- Chemical Synthesis and Analysis
- Lipid Membrane Structure and Behavior
- Caveolin-1 and cellular processes
- Neurogenesis and neuroplasticity mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Nerve injury and regeneration
Oregon Health & Science University
2014-2024
VA Portland Health Care System
2015-2024
Vollum Institute
1988-2022
Case Western Reserve University
2022
University of Colorado Anschutz Medical Campus
2022
New York University Abu Dhabi
2022
Portland VA Medical Center
1998-2020
National Institutes of Health
2020
Yale University
2020
Harvard University
1993-2020
There is evidence for strong functional antagonistic interactions between adenosine A2A receptors (A2ARs) and dopamine D2 (D2Rs). Although a close physical interaction both has recently been shown using co-immunoprecipitation co-localization assays, the existence of A2AR-D2R protein-protein still had to be demonstrated in intact living cells. In present work, fluorescence resonance energy transfer (FRET) bioluminescence (BRET) techniques were used confirm occurrence co-transfected The degree...
We characterized the effects of drugs on uptake [3H]neurotransmitter by and binding [125I](3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester ([125I]RTI-55) to recombinant human dopamine (hDAT), serotonin (hSERT), or norepinephrine (hNET) transporters stably expressed in embryonic kidney 293 cells. RTI-55 had similar affinity for hDAT hSERT lower hNET (Kd = 1. 83, 0.98, 12.1 nM, respectively). Kinetic analysis [125I]RTI-55 indicated that dissociation rate (k-1) was significantly...
An aspartate residue corresponding to aspartate-80 of dopamine D2 receptors is strictly conserved among that couple guanine nucleotide-binding proteins. Mutation this alters the function several classes neurotransmitter receptors. Dopamine protein Gi inhibit adenylyl cyclase (ATP-pyrophosphate-lyase, cyclizing; EC 4.6.1.1). Like other Gi-coupled receptors, binding agonists and some antagonists sensitive pH sodium. In present report, we demonstrate substitution an alanine or glutamate for...
A human dopamine transporter cDNA was cloned and transfected into COS-7 cells, a cell line that lacks vesicular storage release mechanisms. Cells expressing the acquired capacity to take up via transporter. Ionic conditions stimulate inside-out transport in vivo, such as depolarizing concentrations of K+ or low extracellular Na+, were found Ca(2+)-independent [3H]dopamine from cells. Dopamine uptake inhibitors had one three effects on transporter-mediated efflux. Some drugs, addition...
We demonstrate here that this protein is a functional receptor, i.e. it couples to G-proteins inhibit CAMP generation and hormone secretion.
Abstract: Four dopamine D2 receptor mutants were constructed, in each of which an alanine residue was substituted for one four conserved serine residues, i.e., Ser‐193, Ser‐194, Ser‐197, and Ser‐391. Wild‐type mutant receptors expressed transiently COS‐7 cells stably C6 glioma analysis ligand‐receptor interactions. In radioligand binding assays, the affinity decreased 50‐fold by substitution implicating this dopamine. Each had smaller decreases or more ligands tested, with no apparent...
Using the sequence homology approach for cloning related genes within G-protein-coupled receptor gene family, we have cloned rat beta 1-adrenergic (beta 1-AR). The was isolated from a lambda EMBL3 genomic DNA library using hamster 2-adrenergic 2-AR) coding as probe under low stringency hybridization conditions. 1-AR encodes protein of 466 amino acids that contains one consensus site N-linked glycosylation (Asn-15) and three sites cAMP-dependent kinase phosphorylation (Ser-296, Ser-301,...
Apoptotic pathways and DNA synthesis are activated in neurons the brains of individuals with Alzheimer disease (AD). However, signaling mechanisms that mediate these events have not been defined. We show expression familial AD (FAD) mutants amyloid precursor protein (APP) primary culture causes apoptosis synthesis. Both mediated by p21 kinase PAK3, a serine-threonine interacts APP. A dominant-negative mutant PAK3 inhibits neuronal synthesis; this effect is abolished deletion APP-binding...
Dopamine D2 receptors are members of the G protein-coupled receptor superfamily and expressed on both neurons astrocytes. Using rat C6 glioma cells stably expressing D2L receptor, we show here that dopamine (DA) can activate extracellular signal-regulated kinase (ERK) c-Jun NH2-terminal (JNK) pathways through a mechanism involving receptor-G protein complexes Ras GTP-binding protein. Agonist binding to rapidly activated kinases within 5 min, reached maximum between 10 15 then gradually...
Prolonged stimulation of Gi-coupled receptors often sensitizes adenylate cyclase to subsequent activation by forskolin or Gs-coupled receptors. To identify mechanisms heterologous sensitization, we characterized sensitization cAMP accumulation that was induced recombinant dopamine D2 expressed in C6 glioma and human embryonic kidney (HEK)293 cells. Pretreatment with other agonists for 2 hr blocked the antagonist spiperone but not beta-adrenergic receptor propranolol. Sensitization evident...
The existence of two molecular forms D2 dopamine receptors suggests that differences in the distribution or regulation could be exploited for pharmacological treatment disease. Using probes selective each alternatively spliced variant receptor mRNA, we determined both variants were widely distributed rat brain and pituitary but ratio varied among regions. mRNA 444-amino acid-long variant, D2(444), was most abundant form neostriatum. Intermediate levels D2(444) short form, D2(415), detected...
The distribution and pharmacology of the binding [125I]epidepride, a substituted benzamide with high affinity selectivity for dopamine (DA) D2 receptors in rat brain (Neve et al., J. Pharmacol. Exp. Ther. 252: 1108-1116, 1990), is described human brain. Saturation analysis [125I]epidepride to membranes derived from striatum regions cortex demonstrated similar Kd values (34 28-33 pM, respectively) but differing maximum density site (152 3-8 fmol/mg protein, respectively). pharmacological...
In tissues with two classes of binding sites for a drug, it is common to estimate the proportion each class site by inhibiting radioligand selective unlabeled ligand. Accurate estimates density site, however, will be obtained only if nonselective or used at concentration that saturates both sites. A method simultaneous regression analysis multiple inhibition curves, using program MLAB on PROPHET system, was quantify selectivity radioligands beta-1 beta-2 adrenergic receptors. The...
Mutations in the methyl-CpG-binding protein 2 (MeCP2) result Rett syndrome (RTT), an X-linked disorder that disrupts neurodevelopment. Girls with RTT exhibit motor deficits similar to those Parkinson's disease, suggesting defects nigrostriatal pathway. This study examined age-dependent changes dopamine neurons of substantia nigra (SN) from wild-type, presymptomatic, and symptomatic Mecp2 +/− mice. + SN mice were indistinguishable morphology, resting conductance, current density wild-type...