A5086864255- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Insect and Pesticide Research
- Neuropeptides and Animal Physiology
- Photoreceptor and optogenetics research
- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- Pharmacological Receptor Mechanisms and Effects
- Inflammasome and immune disorders
- Neurobiology and Insect Physiology Research
- Pain Mechanisms and Treatments
- Neuroscience of respiration and sleep
- Adenosine and Purinergic Signaling
- Vagus Nerve Stimulation Research
- Olfactory and Sensory Function Studies
- Hearing, Cochlea, Tinnitus, Genetics
- Neuroendocrine regulation and behavior
- Chemical synthesis and alkaloids
- Cancer Treatment and Pharmacology
- Antimicrobial Peptides and Activities
- Asthma and respiratory diseases
University of Utah
2016-2025
George E. Wahlen Department of VA Medical Center
2015-2024
Hainan University
2019
Johns Hopkins University
2017
University of Pennsylvania
2003-2015
Purdue University West Lafayette
2013-2015
Universidad Autónoma de Madrid
1998-2015
Hospital Clínico San Carlos
2015
Barrow Neurological Institute
2015
National Centre of Scientific Research "Demokritos"
2015
To paralyze their more agile prey, the venomous fish-hunting cone snails ( Conus ) have developed a potent biochemical strategy. They produce several classes of toxic peptides (conotoxins) that attack series successive physiological targets in neuromuscular system fish. The include presynaptic ω-conotoxins prevent voltage-activated entry calcium into nerve terminal and release acetylcholine, postsynaptic α-conotoxins inhibit acetylcholine receptor, muscle sodium channel inhibitors,...
Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic (DA) neurons have long been considered as potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine and cocaine addiction or Parkinson's disease. However, DA express mRNAs coding most, if not all, neuronal nAChR subunits, subunit composition functional nAChRs has difficult to establish. Immunoprecipitation experiments performed on mouse striatal extracts allowed us identify...
We have isolated a 16-amino acid peptide from the venom of marine snail Conus magus which potently blocks nicotinic acetylcholine receptors (nAChRs) composed α3β2 subunits. This peptide, named α-conotoxin MII, was identified by electrophysiologically screening fractions against cloned expressed in Xenopus oocytes. The peptide's structure, has been confirmed mass spectrometry and total chemical synthesis, differs significantly those all previously α-conotoxins. Disulfide bridging, however, is...
Pharmacological evaluation of nicotine-stimulated dopamine release from striatum has yielded data consistent with activation a single population nicotinic acetylcholine receptors (nAChR). However, discovery that α-conotoxin MII (α-CtxMII) partially inhibits the response indicates two classes presynaptic nAChRs mediate release. We have investigated pharmacology and subunit composition these nAChR. Inhibition mouse striatal synaptosomes by α-CtxMII occurs within minutes; recovery is slow. The...
Neuronal nicotinic acetylcholine receptors (nAChRs) expressed on mesostriatal dopaminergic neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Using immunoprecipitation ligand-binding techniques, we have shown that both alpha6beta2* alpha4(nonalpha6)beta2* nAChRs in the caudate-putamen only alpha6* can bind alpha-conotoxin MII methyllycaconitine with affinities 1.3 40 nm, respectively. Further studies performed...
The omega-conotoxins from the venom of fish-hunting cone snails are probably most useful presently available ligands for neuronal Ca channels vertebrates. Two these peptide toxins, MVIIA and MVIIB Conus magus, were purified. amino acid sequences show significant differences geographus. Total synthesis omega-conotoxin was achieved, biologically active radiolabeled toxin produced by iodination. Although C. geographus (GVIA) magus (MVIIA) appear to compete same sites in mammalian brain,...
The identification of the molecular mechanisms involved in nicotine addiction and its cognitive consequences is a worldwide priority for public health. Novel vivo paradigms were developed to match this aim. Although β2 subunit neuronal nicotinic acetylcholine receptor (nAChR) has been shown play crucial role mediating reinforcement properties nicotine, little known about contribution different α partners (i.e., α4 α6), homo-pentameric α7, brain areas other than ventral tegmental area (VTA)...
The alpha6 subunit of the nicotinic acetylcholine receptor (nAChR) is expressed at very high levels in dopaminergic (DA) neurons. However, because lack pharmacological tools selective for alpha6-containing nAChRs, role this etiology nicotine addiction remains unknown. To provide new to investigate issue, we generated an nAChR knock-out mouse. Homozygous null mutants (alpha6-/-) did not exhibit any gross neurological or behavioral deficits. A careful anatomic and molecular examination...
Neuronal nicotinic acetylcholine receptors (nAChRs) with putative α3β4-subunits have been implicated in the mediation of signaling various systems, including ganglionic transmission peripherally and nicotine-evoked neurotransmitter release centrally. However, progress characterization these has hampered by a lack α3β4-selective ligands. In this report, we describe purification an α3β4 nAChR antagonist, α-conotoxin AuIB, from venom “court cone,” Conus aulicus. We also total chemical synthesis...
α9α10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except the case auditory system, function nAChRs is not known. Here we show that selective block (rather than stimulation) analgesic an animal model nerve injury pain. In addition, blockade this nAChR subtype reduces number choline acetyltransferase-positive cells, macrophages, at site injury. Chronic neuropathic pain estimated to affect up 8% world's...
Nigrostriatal dopaminergic neurons express many nicotinic acetylcholine receptor (nAChR) subunits capable of forming multiple nAChR subtypes. These subtypes are expressed differentially along the neuron and presumably mediate diverse responses. beta3 subunit mRNA has restricted expression but is abundant in substantia nigra ventral tegmental areas. To investigate potential role(s) receptors containing tracts, we generated mice with a null mutation gene. We were thereby able to identify...
The venom of a fish-hunting cone snail (Conus geographus) contains novel toxin, the "sleeper" peptide, which induces sleep-like state in mice when injected intracerebrally.We demonstrate that this peptide 5 mol y-carboxyglutamate (Gla) 17 amino acids.The acid sequence sleeper isGly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2.We have described isolation and properties variety toxins from venoms two piscivorous snails, Conus geogruphus Linn.and C. magus...
Activation of presynaptic nicotinic acetylcholine receptors (nAChRs) can induce the release neurotransmitters such as dopamine and norepinephrine in CNS. Accumulating evidence suggests that distinct nAChR subtypes are involved; however, it has been difficult to determine subunit composition these receptors, part because lack a sufficient variety selective ligands. We present experimental data at least two different complexes involved release, one which an α3/β2 interface. The recently...
Neuronal nicotinic acetylcholine receptors (nAChRs) both mediate direct cholinergic synaptic transmission and modulate by other neurotransmitters. Novel ligands are needed as probes to discriminate among structurally related nAChR subtypes. α-Conotoxin MII, a selective ligand that discriminates variety of subtypes, fails well between some subtypes containing the closely α3 α6 subunits. Structure-function analysis α-conotoxin MII was performed in an attempt generate analogs with preference...
W e report the isolation, characterization, and total synthesis of a small peptide ligand for nicotinic acetylcholine receptors (nAChRs).It is highly active against neuromuscular receptor in frog but not mice.In contrast, it induces seizures when injected centrally mice rats, suggesting that may target neuronal nAChRs mammals.Although such be important both normal cognition pathophysiology several neuropsychiatric disorders, there are few ligands to discriminate between multiple subtypes.The...
The α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the α9α10 nAChR subtype. This is believed mediate cholinergic synaptic transmission between efferent olivocochlear fibers hair cells of cochlea. In addition and/or expression has been described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes, pars tuberalis pituitary. Specific antagonists that selectively block channel could be valuable tools for elucidating its role these diverse tissues....