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Full-Text Articles in Medicine and Health Sciences

Topographic Plasticity In Primary Visual Cortex Is Mediated By Local Corticocortical Connections, Mike B. Calford, Layne L. Wright, Andrew B. Metha, Vivian Taglianetti Jan 2003

Topographic Plasticity In Primary Visual Cortex Is Mediated By Local Corticocortical Connections, Mike B. Calford, Layne L. Wright, Andrew B. Metha, Vivian Taglianetti

Illawarra Health and Medical Research Institute

The placement of monocular laser lesions in the adult cat retina produces a lesion projection zone (LPZ) in primary visual cortex (V1) in which the majority of neurons have a normally located receptive field (RF) for stimulation of the intact eye and an ectopically located RF ( displaced to intact retina at the edge of the lesion) for stimulation of the lesioned eye. Animals that had such lesions for 14 - 85 d were studied under halothane and nitrous oxide anesthesia with conventional neurophysiological recording techniques and stimulation of moving light bars. Previous work suggested that a candidate source of …


Allosteric Α1-Adrenoreceptor Antagonism By The Conopeptide Ρ-Tia, Iain A. Sharpe, Linda Thomas, Marion L. Loughnan, Leonid Motin, Elka Palant, Daniel E. Croker, Dianne Alewood, Songhai Chen, Robert M. Graham, Paul F. Alewood, David J. Adams, Richard J. Lewis Jan 2003

Allosteric Α1-Adrenoreceptor Antagonism By The Conopeptide Ρ-Tia, Iain A. Sharpe, Linda Thomas, Marion L. Loughnan, Leonid Motin, Elka Palant, Daniel E. Croker, Dianne Alewood, Songhai Chen, Robert M. Graham, Paul F. Alewood, David J. Adams, Richard J. Lewis

Illawarra Health and Medical Research Institute

A peptide contained in the venom of the predatory marine snail Conus tulipa, ρ-TIA, has previously been shown to possess α 1,-adrenoreceptor antagonist activity. Here, we further characterize its pharmacological activity as well as its structure-activity relationships. In the isolated rat vas deferens, ρ-TIA inhibited α1, -adrenoreceptor-mediated increases in cytosolic Ca2+ concentration that were triggered by norepinephrine, but did not affect presynaptic α2-adrenoreceptor-mediated responses. In radioligand binding assays using [125I]HEAT, ρ-TIA displayed slightly greater potency at the α1B, than at the α1A or α1D, subtypes. Moreover, although it did not affect the rate of association for [3H]prazosin binding to the …


Inhibition Of The Norepinephrine Transporter By The Venom Peptide Χ-Mria: Site Of Action, Na+ Dependence, And Structure-Activity Relationship, Iain A. Sharpe, Elka Palant, Christina I. Schroeder, David M. Kaye, David J. Adams, Paul F. Alewood, Richard J. Lewis Jan 2003

Inhibition Of The Norepinephrine Transporter By The Venom Peptide Χ-Mria: Site Of Action, Na+ Dependence, And Structure-Activity Relationship, Iain A. Sharpe, Elka Palant, Christina I. Schroeder, David M. Kaye, David J. Adams, Paul F. Alewood, Richard J. Lewis

Illawarra Health and Medical Research Institute

χ-Conopeptide MrIA (χ-MrIA) is a 13-residue peptide contained in the venom of the predatory marine snail Conus marmoreus that has been found to inhibit the norepinephrine transporter (NET). We investigated whether χ-MrIA targeted the other members of the monoamine transporter family and found no effect of the peptide (100 μM) on the activity of the dopamine transporter and the serotonin transporter, indicating a high specificity of action. The binding of the NET inhibitors, [3H]nisoxetine and [ 3H]mazindol, to the expressed rat and human NET was inhibited by χ-MrIA with the conopeptide displaying a slight preference toward the rat isoform. For …


Α-Conotoxins Pnia And [A10l]Pnia Stabilize Different States Of The Α7-L247t Nicotinic Acetylcholine Receptor, Ron C. Hogg, Gene Hopping, Paul F. Alewood, David J. Adams, Daniel Bertrand Jan 2003

Α-Conotoxins Pnia And [A10l]Pnia Stabilize Different States Of The Α7-L247t Nicotinic Acetylcholine Receptor, Ron C. Hogg, Gene Hopping, Paul F. Alewood, David J. Adams, Daniel Bertrand

Illawarra Health and Medical Research Institute

The effects of the native α-conotoxin PnIA, its synthetic derivative [A10L]PnIA and alanine scan derivatives of [A10L]PnIA were investigated on chick wild type α7 and α7-L247T mutant nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes. PnIA and [A10L]PnIA inhibited acetylcholine (ACh)-activated currents at wtα7 receptors with IC50 values of 349 and 168 nM, respectively. Rates of onset of inhibition were similar for PnIA and [A10L]PnIA; however, the rate of recovery was slower for [A10L]PnIA, indicating that the increased potency of [A10L]PnIA at α7 receptors is conveyed by its slower rate of dissociation from the receptors. All the alanine mutants of …


Isolation, Structure, And Activity Of Gid, A Novel Α4/7-Conotoxin With An Extended N-Terminal Sequence, Annette Nicke, Marion L. Loughnan, Emma L. Millard, Paul F. Alewood, David J. Adams, Norelle L. Daly, David J. Craik, Richard J. Lewis Jan 2003

Isolation, Structure, And Activity Of Gid, A Novel Α4/7-Conotoxin With An Extended N-Terminal Sequence, Annette Nicke, Marion L. Loughnan, Emma L. Millard, Paul F. Alewood, David J. Adams, Norelle L. Daly, David J. Craik, Richard J. Lewis

Illawarra Health and Medical Research Institute

Using assay-directed fractionation of Conus geographus crude venom, we isolated α-conotoxin GID, which acts selectively at neuronal nicotinic acetylcholine receptors (nAChRs). Unlike other neuronally selective α-conotoxins, α-GID has a four amino acid N-terminal tail, γ-carboxyglutamate (Gla), and hydroxyproline (O) residues, and lacks an amidated C terminus. GID inhibits α7 and α3β2 nAChRs with IC50 values of 5 and 3 nM, respectively and is at least 1000-fold less potent at the α1β1γδ, α3β4, and α4β4 combinations. GID also potently inhibits the α4β2 subtype (IC50 of 150 nM). Deletion of the N-terminal sequence (GIDΔ1-4) significantly decreased activity at the α4β2 nAChR but …