A short pre-conception bout of predation risk affects both children and grandchildren.

Traumatic events that affect physiology and behavior in the current generation may also impact future generations. We demonstrate that an ecologically realistic degree of predation risk prior to conception causes lasting changes in the first filial (F1) and second filial (F2) generations. We exposed male and female mice to a live rat (predator stress) or control (non-predator) condition for 5 min.

Modelling of -tyramine transport across human intestinal epithelial cells predicts the presence of additional transporters.

-Tyramine (TYR) is an endogenous trace amine, which can also be synthesized by intestinal microbiota, and is present in commonly consumed diets. TYR is an agonist for the intracellular trace amine-associated receptor 1, which has been implicated in psychiatric, metabolic, and immune-related disorders. We have previously demonstrated TYR readily diffuses across lipid bilayers, while transport across Caco-2 cell membranes involves Organic Cation Transporter 2 (OCT2) and a Na-dependent active transporter.

TAAR1 Regulates Purinergic-induced TNF Secretion from Peripheral, But Not CNS-resident, Macrophages.

Trace amine-associated receptor 1 (TAAR1) is an established neuroregulatory G protein-coupled receptor with recent studies suggesting additional functions related to immunomodulation. Our lab has previously investigated TAAR1 expression within cells of the innate immune system and herein we aim to further elucidate TAAR1 function in both peripherally-derived and CNS-resident macrophages. The selective TAAR1 agonist RO5256390 was used in combination with common damage associated molecular patterns (ATP and ADP) to observe the effect of TAAR1 agonism on modulating cytokine secretion and metabolic profiles.

The Use of Seahorse XF Assays to Interrogate Real-Time Energy Metabolism in Cancer Cell Lines.

The propensity of cancer cells to preferentially undergo anaerobic metabolism despite oxygen being abundant is referred to as the Warburg effect. Measuring cellular metabolism is therefore central to understanding the cellular physiology of cancer cells. The Seahorse XFe Analyzer series allows real-time measurement of cellular metabolism.

Culture of Adherent Cancer Cell Lines.

Adherent cell lines grow attached to the surface of a cell culture vessel. Due to the adherent nature of the cells, enzymes, such as trypsin, are required to lift the cells from the cell culture vessel for harvesting or subculturing. Many cancer cell lines are adherent, rendering adherent cell culture a critical experimental method in the fields of cell biology, biochemistry, and cancer research.

TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation.

TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue.

Involvement of Organic Cation Transporter 2 and a Na-dependent active transporter in p-tyramine transport across Caco-2 intestinal cells.

Aims: We have previously demonstrated that p-tyramine (TYR), an endogenous trace amine-associated receptor 1 agonist, passage across neuronal membranes involves a transporter exhibiting the pharmacological profile of Organic Cation Transporter 2 (OCT2). Since TYR is also a constituent of foodstuffs and produced by the intestinal microbiota, here we have investigated whether similar processes are involved in the passage of 100 nM TYR across apical and basolateral membranes of the Caco-2 human intestinal epithelial cell line.

Materials And Methods: [H]TYR transport across apical and basolateral membranes of Caco-2 cell monolayers was measured in the presence of inhibitors of TYR metabolizing enzymes.

Identification of a subset of trace amine-associated receptors and ligands as potential modulators of insulin secretion.

The worldwide prevalence of diabetes has reached 8.5% among adults, and this is characterised by elevated glucose concentrations and failing insulin secretion. Furthermore, most people with type 2 diabetes are either obese or overweight, with the associated dyslipidaemia contributing to the development of insulin resistance and increased cardiovascular risk.

TAAR1 levels and sub-cellular distribution are cell line but not breast cancer subtype specific.

Trace amine-associated receptors are G protein-coupled receptors of which TAAR1 is the most well-studied. Recently, Vattai et al. (J Cancer Res Clin Oncol 143:1637-1647 https://doi.

Trace Amine-Associated Receptors as Novel Therapeutic Targets for Immunomodulatory Disorders.

Trace amines and their receptors (trace amine-associated receptors; TAARs) are an emerging pharmacological target for the treatment of human disorders. While most studies have focused on their therapeutic potential for neurologic and psychiatric disorders, TAARs are also expressed throughout the periphery, including prominent expression in human leukocytes. Furthermore, recent independent, unbiased metabolomic studies have consistently identified one or more TAAR ligands as potential etiologic factors in inflammatory bowel disease (IBD).

Trace Amines and Their Receptors.

Trace amines are endogenous compounds classically regarded as comprising -phenylethyalmine, -tyramine, tryptamine, -octopamine, and some of their metabolites. They are also abundant in common foodstuffs and can be produced and degraded by the constitutive microbiota. The ability to use trace amines has arisen at least twice during evolution, with distinct receptor families present in invertebrates and vertebrates.

Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges.

The discovery in 2001 of a G protein-coupled receptor family, subsequently termed trace amine-associated receptors (TAAR), triggered a resurgence of interest in so-called trace amines. Initial optimism quickly faded, however, as the TAAR family presented a series of challenges preventing the use of standard medicinal chemistry and pharmacology technologies. Consequently the development of basic tools for probing TAAR and translating findings from model systems to humans has been problematic.

Pharmacological characterization of a high-affinity p-tyramine transporter in rat brain synaptosomes.

p-Tyramine is an archetypal member of the endogenous family of monoamines known as trace amines, and is one of the endogenous agonists for trace amine-associated receptor (TAAR)1. While much work has focused on the function of TAAR1, very little is known about the regulation of the endogenous agonists. We have previously reported that p-tyramine readily crosses lipid bilayers and that its release from synaptosomes is non-exocytotic.

Membrane permeability of trace amines: evidence for a regulated, activity-dependent, nonexocytotic, synaptic release.

Both pre- and post-synaptic effects of trace amines have been demonstrated. The putative intracellular location of Trace Amine-Associated Receptors necessitate that membrane transport processes be present in order for post-synaptic effects to occur. Here we examine the ability of trace amines to cross synthetic (Fluorosomes) and native (synaptosomes) lipid bilayer membranes.

Molecular dynamics-based simulation of trace amine membrane permeability.

Trace amines are endogenous compounds, typified by 2-phenylethylamine (PE) and p-tyramine (TA), found in the vertebrate central nervous system. Although synthesized in pre-synaptic terminals, trace amines do not appear to act as neurotransmitters, but rather modulate responsivity to co-existing neurotransmitters. Trace amines are neither actively accumulated in synaptic vesicles, nor released in an activity-dependent manner.

The effects of pargyline and 2-phenylethylamine on D1-like dopamine receptor binding.

2-Phenylethylamine (PE) potentiates neuronal responses to dopamine by an unknown post-synaptic mechanism. Here, whether PE modifies D1-like receptor binding was examined. An unexpected effect of the monoamine oxidase inhibitor pargyline was observed, which did not involve competition for ligand binding.

Glyceraldehyde-3-phosphate dehydrogenase as a target for small-molecule disease-modifying therapies in human neurodegenerative disorders.

Recent articles have highlighted numerous additional functions of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that are independent of its well-documented glycolytic function. One of the most intriguing of these functions is as an initiator of programmed cell death cascades. This activity involves a nuclear appearance of GAPDH, a considerable proportion of which requires synthesis of new GAPDH protein and has characteristics suggesting the involvement of a novel isozyme.

Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators.

The presence of the so-called trace amines 2-phenylethylamine, m-tyramine, p-tyramine, m-octopamine, p-octopamine and tryptamine in the mammalian central nervous system has been known for several decades. Despite much initial interest, these amines have largely been thought of as little more than metabolic by-products. The recent description of a family of mammalian trace amine receptors has, however, seen a resurgence of interest in the physiological role of this class of compounds.

On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site, and effects thereby elicited.

Many inhibitors of monoamine oxidase, particularly those developed during the past three decades, are often referred to as being "selective" for one or other isoform of the enzyme. However true this may be, selectivity within the EC 1.4.

Apoptotic signaling cascades.

Apoptosis is a form of programmed cell death that results in the orderly and efficient removal of damaged or unnecessary cells, such as those resulting from DNA damage or during development. There are many factors that contribute to this process, each demonstrating specificity of function, regulation, and pathway involvement. The aim of this brief overview is to provide an introduction to a number of these factors as well as the various apoptotic pathways that have been identified.