Search results for "Tropic"

ADAM-10 over-expression increases cortical synaptogenesis.

2006

Cortical cholinergic, glutamatergic and GABAergic terminals become upregulated during early stages of the transgenic amyloid pathology. Abundant evidence suggests that sAPP alpha, the product of the non-amyloidogenic alpha-secretase pathway, is neurotrophic both in vitro and when exogenously applied in vivo. The disintegrin metalloprotease ADAM-10 has been shown to have alpha-secretase activity in vivo. To determine whether sAPP alpha has an endogenous biological influence on cortical presynaptic boutons in vivo, we quantified cortical cholinergic, glutamatergic and GABAergic presynaptic bouton densities in either ADAM-10 moderate expressing (ADAM-10 mo) transgenic mice, which moderately ov…

Exploring kainate receptor pharmacology using molecular dynamics simulations.

2010

Ionotropic glutamate receptors (iGluRs) are enticing targets for pharmaceutical research; however, the search for selective ligands is a laborious experimental process. Here we introduce a purely computational procedure as an approach to evaluate ligand–iGluR pharmacology. The ligands are docked into the closed ligand-binding domain and during the molecular dynamics (MD) simulation the bi-lobed interface either opens (partial agonist/antagonist) or stays closed (agonist) according to the properties of the ligand. The procedure is tested with closely related set of analogs of the marine toxin dysiherbaine bound to GluK1 kainate receptor. The modeling is set against the abundant binding data …

Choline is a Selective Agonist of α7 Nicotinic Acetylcholine Receptors in the Rat Brain Neurons

1998

In the present study, we demonstrate that choline, a precursor of acetylcholine (ACh) and a product of acetylcholine hydrolysis by acetylcholinesterase (AChE), acts as an efficient and relatively selective agonist of alpha7-containing nicotinic acetylcholine receptors (nAChR) in neurons cultured from the rat hippocampus, olfactory bulb and thalamus as well as in PC12 cells. Choline was able to activate postsynaptic and presynaptic alpha7 nAChRs, with the latter action resulting in the release of other neurotransmitters. Although choline was approximately one order of magnitude less potent than ACh (EC50 of 1.6 mM for choline and 0.13 mM for ACh), it acted as a full agonist at alpha7 nAChRs.…

Structural Mechanism of N-Methyl-D-Aspartate Receptor Type 1 Partial Agonism

2012

N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that contribute to the signal transmission in the central nervous system. NMDA receptors are heterotetramers that usually consist of two GluN1 and GluN2 monomers. The extracellular ligand-binding domain (LBD) of a monomer is comprised of discontinuous segments that form the functional domains D1 and D2. While the binding of a full agonist glycine to LBD of GluN1 is linked to cleft closure and subsequent ion-channel opening, partial agonists are known to activate the receptor only sub-maximally. Although the crystal structures of the LBD of related GluA2 receptor explain the mechanism for the partial a…

Activation of phospholipases C and D by the novel metabotropic glutamate receptor agonist tADA.

1997

Abstract In hippocampal slices taken from 8-day-old rats, trans-azetidine-2,4-dicarboxylic acid (tADA), a novel glutamatergic agonist acting preferentially at class I mGluR receptors, activates phosphoinositide and phosphatidylcholine hydrolysis with widely different potencies. Inositol phosphate formation was maximally increased at 10 μM tADA ( ec 50: 1.2 μM), while phospholipase D activation was observed at a tADA concentration of 1 mM. This is the first report of a tADA-induced phospholipase D activity. © 1997 Elsevier Science Ltd. All rights reserved.

Modulatory effects of the novel TrkB receptor agonist 7,8-dihydroxyflavone on synaptic transmission and intrinsic neuronal excitability in mouse visu…

2013

7,8-Dihydroxyflavone (7,8 DHF) is a new recently identified TrkB receptor agonist, which possesses a potent neurotrophic activity and shares many physiological properties with the neurotrophin "Brain Derived Neurotrophic Factor" (BDNF). However, its precise mechanism of action at the cellular level has not been clarified yet. In the present study we explored the effects of this agent on synaptic and intrinsic neuronal properties by performing whole-cell patch clamp recordings from layer 2/3 pyramidal neurons. Incubation of acute cortical slices with 7,8-DHF (20 µM) for 30 min caused a selective reduction in the strength of GABAergic inhibition. The amplitude of evoked inhibitory postsynapti…

Ontogenetic and Pharmacological Studies on Metabotropic Glutamate Receptors Coupled to Phospholipase D Activation

1997

The present study was aimed at characterizing the metabotropic receptor subtype which is involved in the activation of phospholipase D (PLD) by glutamate in rat hippocampal slices. We first observed that the ontogenetic profile of glutamate-induced hydrolysis of phosphoinositides and of phosphatidylcholine was strikingly similar. Both pathways were significantly activated by glutamate in tissue taken from 3-, 8- and 15-day old rats, but not in adult rats. PLD activation was strongest in slices taken from 8-day old rats. At this age, quisqualate had a higher potency for PLD activation (EC50: 0.6 microM) than 1S,3R-ACPD (EC50: 16 microM) and DHPG, a specific activator of group I mGluR, was a …

Aldosterone synthase activity in the Y-1 adrenal cell line.

1995

The Y-1 adrenal cell line was shown to produce 20 alpha-dihydroaldosterone from deoxycorticosterone. This compound was identified by GC-MS by comparison with the previously synthesized reference compound. Two other 18-hydroxylated metabolites were identified as 11 beta,18-dihydroxy-20 alpha-dihydroprogesterone from endogenous cholesterol and 18-hydroxy-20 alpha-dihydro-11-dehydrocorticosterone from DOC. The conditions necessary for the synthesis of these compounds are culturing in 20% serum-supplemented medium and repeated incubations with the substrate. The production of 11 beta-hydroxylated steroids and that of 18-oxygenated steroids is stimulated differently by ACTH and angiotensin II su…

A descendent tropical Landau–Ginzburg potential for $\mathbb{P}^2$

2016

Enumerative Aspects of the Gross-Siebert Program

2015

For the last decade, Mark Gross and Bernd Siebert have worked with a number of collaborators to push forward a program whose aim is an understanding of mirror symmetry. In this chapter, we’ll present certain elements of the “Gross-Siebert” program. We begin by sketching its main themes and goals. Next, we review the basic definitions and results of two main tools of the program, logarithmic and tropical geometry. These tools are then used to give tropical interpretations of certain enumerative invariants. We study in detail the tropical pencil of elliptic curves in a toric del Pezzo surface. We move on to a basic illustration of mirror symmetry, Gross’s tropical construction for \(\mathbb{P…