A5088047399- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Pesticide Exposure and Toxicity
- Tryptophan and brain disorders
- Treatment of Major Depression
- Insect and Pesticide Research
- Memory and Neural Mechanisms
- Neuroendocrine regulation and behavior
- Photoreceptor and optogenetics research
- Herpesvirus Infections and Treatments
- Environmental Toxicology and Ecotoxicology
- Pesticide and Herbicide Environmental Studies
- Chemical synthesis and alkaloids
- Anesthesia and Neurotoxicity Research
- Toxin Mechanisms and Immunotoxins
- Stress Responses and Cortisol
- HIV Research and Treatment
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Receptor Mechanisms and Effects
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
University of Maryland, Baltimore
2015-2025
National Institute of Mental Health
2018-2021
National Institutes of Health
2018-2021
Institute on Aging
2018-2021
National Center for Advancing Translational Sciences
2018-2021
National Institute on Aging
2018-2021
Countervail Corporation (United States)
2014-2020
Biomedical Advanced Research and Development Authority
2014
Mitsubishi Tanabe Pharma Corporation
2011
University of Mary
2011
The tryptophan metabolite kynurenic acid (KYNA) has long been recognized as an NMDA receptor antagonist. Here, interactions between KYNA and the nicotinic system in brain were investigated using patch-clamp technique HPLC. In electrophysiological studies, agonists delivered via a U-shaped tube, was applied admixture with background perfusion. Exposure (>/=4 min) of cultured hippocampal neurons to (>/=100 nm) inhibited activation somatodendritic alpha7 nAChRs; IC(50) for approximately 7...
Abstract In the present study, we demonstrate that choline, a precursor of acetylcholine (ACh) and product hydrolysis by acetylcholinesterase (AChE), acts as an efficient relatively selective agonist α7–containing nicotinic receptors (nAChR) in neurons cultured from rat hippocampus, olfactory bulb thalamus well PC12 cells. Choline was able to activate postsynaptic presynaptic α7 nAChRs, with latter action resulting release other neurotransmitters. Although choline approximately one order...
Mr. Chairman, ladies and gentlemen, it is an honor to receive from the American Society of Pharmacology Experimental Therapeutics 1996 Otto Krayer Award sponsored by Zeneca Pharmaceutics Co. I am especially delighted this award not only because remarkable contributions that
Neuronal nicotinic receptors (nAChR) are known to control transmitter release in the CNS. Thus, this study was aimed at exploring diversity and localization of nAChRs present CA1 interneurons rat hippocampal slices. The use a U-tube as agonist delivery system critical for reliable detection responses induced by brief exposure neurons ACh or alpha7 nAChR-selective choline. demonstrated that interneurons, addition expressing functional nAChRs, also express alpha4beta2-like activation both...
Galantamine (Reminyl), an approved treatment for Alzheimer9s disease (AD), is a potent allosteric potentiating ligand (APL) of human α3β4, α4β2, and α6β4 nicotinic receptors (nAChRs), the chicken/mouse chimeric α7/5-hydroxytryptamine<sub>3</sub> receptor, as was shown by whole-cell patch-clamp studies embryonic kidney-293 cells stably expressing single nAChR subtype. potentiates agonist responses four subtypes studied in same window concentrations (i.e., 0.1–1 μM), which correlates with...
Cholinergic control of the activity human cerebral cortical circuits has long been thought to be accounted for by interaction acetylcholine (ACh) with muscarinic receptors. Here we report discovery functional nicotinic receptors (nAChRs) in interneurons cortex and discuss physiological clinical implications these findings. The whole-cell mode patch-clamp technique was used record responses triggered U-tube application nonselective agonist ACh alpha7-nAChR-selective choline visualized means...
Methyllycaconitine, a toxin isolated from the seeds of Delphinium brownii, inhibited acetylcholine- and anatoxin-induced whole-cell currents in cultured fetal rat hippocampal neurons, at picomolar concentrations. This antagonism was specific, concentration dependent, reversible, voltage independent. Furthermore, methyllycaconitine 125I-alpha-bungarotoxin binding to adult membranes, protected against alpha-bungarotoxin-induced pseudoirreversible blockade nicotinic currents, shifted...
ACh receptors sensitive to nicotine (nAChR) are present in human skin keratinocytes and bronchial epithelial cells. They stimulated by secreted the same cells that express them, they modulate cell motility shape. A variety of non-neuronal tissues, including endothelial cells, synthesize ACh, which raises possibility nicotine. We demonstrate here line blood vessels functional nAChRs. Their structure ion-gating properties similar those nAChRs expressed ganglionic neurons In situ hybridization...
We demonstrated previously that human skin keratinocytes express acetylcholine receptors (AChRs) sensitive to and nicotine, which regulate cell adhesion motility. demonstrate here rodent bronchial epithelial cells (BECs) AChRs similar those expressed by some neurons. Patch-clamp experiments the BEC are functional, they activated nicotine. They blocked kappa-bungarotoxin, a specific antagonist of AChR isotypes neurons in ganglia. Their ion-gating properties consistent with ganglia, formed...
Similar to the gamma-aminobutyric acidA receptor and N-methyl-D-aspartate subtype of glutamate receptor, neuronal nicotinic acetylcholine receptors are subject positive modulatory control by allosterically acting ligands. Exogenous ligands such as galanthamine neurotransmitter 5-hydroxytryptamine, when applied in submicromolar concentrations with agonists, significantly increase frequency opening channels potentiate agonist-activated currents. Because these effects have been shown be blocked...
The epithelial or endothelial cells that line the human bronchi and aorta express nicotinic acetylcholine receptors (nAChRs) of α3 subtypes. We report here bronchial (BEC) aortic (AEC) also nAChR α7 subunit, which forms functional nAChRs. Polymerase chain reaction in situ hybridization experiments detected subunit mRNA cultured BEC AEC sections rat trachea. binding radiolabeled α-bungarotoxin revealed a few thousand sites per cell bovine AEC. Western blot immunohistochemistry demonstrated...
The <i>N</i>-methyl-d-aspartate (NMDA) receptor antagonist memantine is an approved drug for treatment of Alzheimer9s disease (AD). Other such treatments are cholinesterase inhibitors and nicotinic acetylcholine (nAChR)-sensitizing agents as galantamine. present study was designed to test whether exerts any effect on the cholinergic system, in particular Ca<sup>2+</sup>-conducting α7<sup>*</sup> nAChR, cultured hippocampal neurons. Memantine caused a concentration-dependent reduction...
Significance Standard antidepressant treatments require weeks to show effectiveness. A single subanesthetic dose of ketamine rapidly attenuates many clinical signs and symptoms depression; however, treatment also has adverse effects, including dissociation potential for abuse, which are mediated by NMDA glutamate receptor (NMDAR) inhibition. Previous work revealed that the metabolite (2 R ,6 )-hydroxynorketamine (HNK) induces antidepressant-like responses in rodents while minimizing effects...
The translational capacity of data generated in preclinical toxicological studies is contingent upon several factors, including the appropriateness animal model. primary objectives this article are: 1) to analyze natural history acute and delayed signs symptoms that develop following an exposure humans organophosphorus (OP) compounds, with emphasis on nerve agents; 2) identify models clinical manifestations human OPs; 3) review mechanisms contribute immediate OP neurotoxicity. As discussed...
In this study, the patch-clamp technique was used to determine effects of galantamine, a cholinesterase inhibitor and nicotinic allosteric potentiating ligand (APL) for treatment Alzheimer9s disease, on synaptic transmission in brain slices. rat hippocampal human cerebral cortical slices, 1 μM acting as APL, increased γ-aminobutyric acid (GABA) release triggered by 10 acetylcholine (ACh). Likewise, an APL presynaptically located receptors (nAChRs) that are tonically active, potentiated...