Tonic Calcium-Activated Chloride Current Sustained by ATP Release and Highly Desensitizing Human P2X1 Receptors.

Extracellular adenosine triphosphate (ATP) participates in maintaining the vascular tone in the CNS, particularly in the retina, via the tonic activity of ligand gated activated P2X1 receptors. P2X1 receptors are characterized by their high affinity for ATP and their strong desensitization to concentrations of ATP that are 200-fold lower than their EC. The mechanism behind P2X1 tonic activity remains unclear.

Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy.

Background: Major depressive disorders are characterized by their severity and long-lasting symptoms, which make such disorders highly disabling illnesses. Unfortunately, 50% of major depressive patients experience relapses, perhaps partly because drug research has been performed only in animal models that screen for antidepressant drugs that appear to only ameliorate acute depression symptoms. The bilateral olfactory bulbectomy (OBX) animal model presents the advantage of mimicking the symptoms of chronic depression by means of brain surgery.

GABAρ selective antagonist TPMPA partially inhibits GABA-mediated currents recorded from neurones and astrocytes in mouse striatum.

The neostriatum plays a central role in motor coordination where nerve cells operate neuronal inhibition through GABAergic transmission. The neostriatum expresses a wide range of GABA-A subunits, including GABAρ1 and ρ2 which are restricted to a fraction of GABAergic interneurons and astrocytes. Spontaneous postsynaptic currents (sPSCs) evoked by 4-aminopyridine (4-AP) were recorded from neurones of the dorsal neostriatum, and their frequency was reduced > 50% by the selective GABAρ antagonist (1,2,5,6-Tetrahydropyridine-4-yl) methylphosphinic acid (TPMPA).

Theobromine-Induced Changes in A1 Purinergic Receptor Gene Expression and Distribution in a Rat Brain Alzheimer's Disease Model.

Dementia caused by Alzheimer's disease (AD) is mainly characterized by accumulation in the brain of extra- and intraneuronal amyloid-β (Aβ) and tau proteins, respectively, which selectively affect specific regions, particularly the neocortex and the hippocampus. Sporadic AD is mainly caused by an increase in apolipoprotein E, a component of chylomicrons, which are cholesterol transporters in the brain. Recent studies have shown that high lipid levels, especially cholesterol, are linked to AD.

Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus.

Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake.

Differential gene expression patterns and colocalization of ATP-gated P2X6/P2X4 ion channels during rat small intestine ontogeny.

Gene coding for ATP-gated receptor ion channels (P2X1-7) has been associated with the developmental process in various tissues; among these ion channel subtypes, P2X6 acts as a physiological regulator of P2X4 receptor functions when the two receptors form heteroreceptors. The P2X4 receptor is involved in pain sensation, the inflammatory process, and body homeostasis by means of Mg(2+) absorption through the intestine. The small intestine is responsible for the absorption and digestion of nutrients; throughout its development, several gene expressions are induced that are related to nutrients received, metabolism, and other intestine functions.

Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons that leads to progressive paralysis of skeletal muscle. Studies of ALS have revealed defects in expression of acetylcholine receptors (AChRs) in skeletal muscle that occur even in the absence of motor neuron anomalies. The endocannabinoid palmitoylethanolamide (PEA) modified the clinical conditions in one ALS patient, improving muscle force and respiratory efficacy.

Dehydration-Induced Anorexia Reduces Astrocyte Density in the Rat Corpus Callosum.

Anorexia nervosa is an eating disorder associated with severe weight loss as a consequence of voluntary food intake avoidance. Animal models such as dehydration-induced anorexia (DIA) mimic core features of the disorder, including voluntary reduction in food intake, which compromises the supply of energy to the brain. Glial cells, the major population of nerve cells in the central nervous system, play a crucial role in supplying energy to the neurons.

Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors.

Ethnopharmacological Relevance: Withania somnifera (WS) has been traditionally used in Ayurvedic medicine as a remedy for debility, stress, nervous exhaustion, insomnia, loss of memory, and to enhance cognitive function. This study provides an empirical evidence to support the traditional use of WS to aid in mental process engaging GABAergic signaling.

Aim Of The Study: We evaluated the effect of aqueous WS root extract (aqWS), and its two main components, withaferin A and withanolide A, on the main inhibitory receptors in the central nervous system: ionotropic GABAA receptors.

Expression of hippocampal serotonin receptors 5-HT2C and 5-HT5A in a rat model of diet-induced obesity supplemented with tryptophan.

Food intake regulation is a complex mechanism that involves endogenous substances and central nervous system structures like hypothalamus or even hippocampus. The neurotransmitter serotonin is distinguished as food intake mediator; within its multiples receptors, the 5-HT2C type is characterized by its inhibitory appetite action but there is no information about 5-HT5A receptors involvement in obesity disease. It is also unknown if there are any changes in the receptors expression in rats hippocampus with induced obesity during development through a high energy diet (HED) supplemented with tryptophan (W).

GABAρ subunits confer a bicuculline-insensitive component to GFAP+ cells of cerebellum.

GABA-A receptors mediating synaptic or extrasynaptic transmission are molecularly and functionally distinct, and glial cells are known to express a plethora of GABA-A subunits. Here we demonstrate that GFAP(+) cells of the granular layer of cerebellum express GABAρ subunits during early postnatal development, thereby conferring peculiar pharmacologic characteristics to GABA responses. Electron microscopy revealed the presence of GABAρ in the plasma membrane of GFAP(+) cells.

Nicotinic and muscarinic agonists and acetylcholinesterase inhibitors stimulate a common pathway to enhance GluN2B-NMDAR responses.

Nicotinic and muscarinic ACh receptor agonists and acetylcholinesterase inhibitors (AChEIs) can enhance cognitive function. However, it is unknown whether a common signaling pathway is involved in the effect. Here, we show that in vivo administration of nicotine, AChEIs, and an m1 muscarinic (m1) agonist increase glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GluN2B)-containing NMDA receptor (NR2B-NMDAR) responses, a necessary component in memory formation, in hippocampal CA1 pyramidal cells, and that coadministration of the m1 antagonist pirenzepine prevents the effect of cholinergic drugs.

Analysis of free ACh and 5-HT in milk from four different species and their bioactivity on 5-HT(3) and nACh receptors.

Milk is one of the most beneficial aliments and is highly recommended in normal conditions; however, in certain disorders, like irritable bowel syndrome, cow milk and dairy products worsen the gastric symptoms and their use is not recommended. Among the most recognized milk-induced gatrointestinal symptoms are abdominal pain, nausea and vomiting, which are processes controlled by cholinergic and serotonergic transmission. Whether the presence of bioavailable ACh and 5-HT in milk may contribute to normal peristalsis, or to the developing of these symptoms, is not known.

TMEM16A alternative splicing isoforms in Xenopus tropicalis: distribution and functional properties.

Oocytes of Xenopus tropicalis elicit a Ca(2+)-dependent outwardly rectifying, low-activating current (ICl,Ca) that is inhibited by Cl(-) channel blockers. When inactivated, ICl,Ca shows an exponentially decaying tail current that is related to currents generated by TMEM16A ion channels. Accordingly, RT-PCR revealed the expression of five alternatively spliced isoforms of TMEM16A in oocytes, which, after expression in HEK-293 cells, gave rise to fully functional Cl(-) channels.

Anion permeation in calcium-activated chloride channels formed by TMEM16A from Xenopus tropicalis.

Calcium-activated chloride channels (CaCC) formed by anoctamin1/TMEM16A subunits are ubiquitously expressed, and these channels are known to prevent polyspermy in amphibian oocytes. Here, we describe a TMEM16A clone isolated from Xenopus tropicalis oocytes (xtTMEM16A) and how the anion permeation properties are modified in single-site mutants of the ion pore. The anion permeability sequence was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate (relative permeabilities 5.

Cloning and characterization of the ionotropic GABA receptor subunit ρ1 from pig (Sus scrofa).

Since human and pig eyes have remarkably anatomical and physiological similitudes swine models have been broadly used for functional studies and therapeutic research. Recently, a GABAρ-mediated relaxation of retinal vascularity suggested that GABAρ signaling may be used to improve retinal blood flow in vascular-driven impaired vision, and a further molecular characterization of GABAρ receptors would be beneficial. However, none of the GABAρ type subunits from pigs has been yet cloned; Among the 19 subunits that compose the family of GABAA receptors, ρ1-3 subunits are capable of forming homomeric channels.

The endogenous GABA bioactivity of camel, bovine, goat and human milks.

GABA orally administered has several beneficial effects on health, including the regulation of hyperglycaemic states in humans. Those effects are similar to the effects reported for camel milk (CMk); however, it is not known whether compounds with GABAergic activity are present in milk from camels or other species. We determined CMk free-GABA concentration by LS/MS and its bioactivity on human GABA receptors.

Characterization of an outward rectifying chloride current of Xenopus tropicalis oocytes.

Here, we describe an outward rectifying current in Xenopus tropicalis oocytes that we have called xtClC-or. The current has two components; the major component is voltage activated and independent of intracellular or extracellular Ca(2+), whereas the second is a smaller component that is Ca(2+) dependent. The properties of the Ca(2+)-independent current, such as voltage dependence and outward rectification, resemble those of ClC anion channels/transporters.

Microtransplantation of cellular membranes from squid stellate ganglion reveals ionotropic GABA receptors.

The squid has been the most studied cephalopod, and it has served as a very useful model for investigating the events associated with nerve impulse generation and synaptic transmission. While the physiology of squid giant axons has been extensively studied, very little is known about the distribution and function of the neurotransmitters and receptors that mediate inhibitory transmission at the synapses. In this study we investigated whether γ-aminobutyric acid (GABA) activates neurotransmitter receptors in stellate ganglia membranes.

A hyperpolarization-activated ion current of amphibian oocytes.

A comparative analysis of a hyperpolarization-activated ion current present in amphibian oocytes was performed using the two-electrode voltage-clamp technique in Xenopus laevis, Xenopus tropicalis, and Ambystoma mexicanum. This current appears to be driven mainly by Cl(-) ions, is independent of Ca(2+), and is made evident by applying extremely negative voltage pulses; it shows a slow activating phase and little or no desensitization. The pharmacological profile of the current is complex.

γ-Aminobutyric acid-ρ expression in ependymal glial cells of the mouse cerebellum.

The ependymal glial cells (EGCs) from the periventricular zone of the cerebellum were studied to determine their distribution and the functional properties of their γ-aminobutyric acid type A (GABA(A) ) receptors. EGCs were identified by the presence of ciliated structures on their ventricular surface and their expression of glial fibrillary acidic protein (GFAP). Interestingly, diverse cell types, including neurons, astrocytes, and other types of glia, were identified in the subventricular zone by their current profiles.

Profiling neurotransmitter receptor expression in the Ambystoma mexicanum brain.

Ability to regenerate limbs and central nervous system (CNS) is unique to few vertebrates, most notably the axolotl (Ambystoma sp.). However, despite the fact the neurotransmitter receptors are involved in axonal regeneration, little is known regarding its expression profile.

GABAρ expression in the medial nucleus of the trapezoid body.

The Calyx of Held (CoH) synapse is the largest synapse in mammals. It is located in the medial nucleus of the trapezoid body (MNTB) and forms part of the auditory pathway. Modest GABAergic signaling is present in the CoH before hearing onset, when glutamatergic transmission predominates.