Natural and synthetic corticosteroids inhibit uptake(2)-mediated transport in CNS neurons.

01:12 EDT 30th June 2015 | BioPortfolio

Summary of "Natural and synthetic corticosteroids inhibit uptake(2)-mediated transport in CNS neurons."

In addition to exerting actions via mineralocorticoid and glucocorticoid receptors, corticosteroids also act by inhibiting uptake(2), a high-capacity monoamine transport system originally described in peripheral tissues. Recent studies have demonstrated that uptake(2) transporters are expressed in the brain and play roles in monoamine clearance, suggesting that they mediate some corticosteroid effects on physiological and behavioral processes. However, the sensitivity of brain uptake(2) to many natural and synthetic corticosteroids has not been characterized. Cultured rat cerebellar granule neurons (CGNs) were previously shown to exhibit corticosterone-sensitive accumulation of the uptake(2) substrate1-methyl-4-phenylpyridinium (MPP(+)). We examined the expression of uptake(1) and uptake(2) transporters in CGNs, and tested the effects of a variety of natural and synthetic corticosteroids on accumulation of [(3)H]-MPP(+) by these cells. Cultured rat CGNs expressed mRNA for three uptake(2)-like transporters: organic cation transporters 1 and 3, and the plasma membrane monoamine transporter. They did not express mRNA for the dopamine or norepinephrine transporters, and expressed very little mRNA for the serotonin reuptake transporter. Accumulation of [(3)H]-MPP(+) by CGNs was dose-dependently inhibited by corticosterone and decynium-22, known inhibitors of uptake(2). Accumulation of MPP(+) was also dose-dependently inhibited, with varying efficacies, by aldosterone, 11-deoxycorticosterone, cortisol, and cortisone, and by the synthetic glucocorticoids betamethasone, dexamethasone and prednisolone, and the glucocorticoid receptor antagonist RU38486. These studies demonstrate that uptake(2) in the CNS is inhibited by a variety of natural and synthetic corticosteroids, and suggest that inhibition of uptake(2)-mediated monoamine clearance may underlie some behavioral and physiological effects of these hormones.

Affiliation

Marquette University, Department of Biomedical Sciences, Milwaukee, WI 53233, USA.

Journal Details

This article was published in the following journal.

Name: Physiology & behavior
ISSN: 1873-507X
Pages: 306-11

Links

PubMed Articles [19711 Associated PubMed Articles listed on BioPortfolio]

Excess Iodide Induces an Acute Inhibition of the Sodium/Iodide Symporter in thyroid rat cells by Increasing Reactive Oxygen Species.

Na(+)/I(-) symporter (NIS) mediates iodide (I(-)) uptake in the thyroid gland, the first and rate limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyro...

Separation of monodisperse alginate nanoparticles and effect of particle size on transport of vitamin E.

Four batches of oleoyl alginate ester (OAE) nanoparticles with narrow size distribution were rapidly separated from the initial batch of nanoparticles by means of centrifugation at the relative centri...

Isolation, biological activity, biosynthesis and synthetic studies towards the rubromycin family of natural products.

Covering from 1953 to 2014The rubromycins are an ever growing family of natural products isolated from various Actinomycetes over the last 60 years. Exhibiting a highly attractive array of antimicrobi...

Fomiroid A, a Novel Compound from the Mushroom Fomitopsis nigra, Inhibits NPC1L1-Mediated Cholesterol Uptake via a Mode of Action Distinct from That of Ezetimibe.

Hypercholesterolemia is one of the key risk factors for coronary heart disease, a major cause of death in developed countries. Suppression of NPC1L1-mediated dietary and biliary cholesterol absorption...

Synthesis of the Putative Structure of 15-Oxopuupehenoic Acid.

A synthesis of the putative structure of the marine natural 15-oxopuupehenoic acid has been achieved starting from commercial (-)-sclareol. Key steps of the synthetic sequence are the Robinson annulat...

Clinical Trials [2021 Associated Clinical Trials listed on BioPortfolio]

Role of Angiotensin II in Insulin-induced Microvascular Activity

In this study we hypothesize infusion of Angiotensin II improves the insulin-induced microvascular dilatation and therefore insulin-mediated glucose uptake. Objectives: Does infusion of An...

Transporter Mediated Uptake of Montelukast

Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair, manufactured by Merck, is a popular LTRA, however its effectiv...

Evaluation of the Versamed iVent in the Transport of Patients Receiving Mechanical Ventilation

The purpose of this study is to evaluate the use of the VersaMed iVent ventilator in the acute care setting, hypothesizing that, in comparison to the standard approach, the use of the Vers...

Dose-Response of Adenosine for Perioperative Pain

Adenosine A1 and A2 receptors are widely distributed in the brain and spinal cord and represent a non-opiate target for pain management. Activated spinal A1 receptors inhibit sensory tran...

The Effect of Alfa-Adrenergic Receptor Blockade on Insulin-Stimulated Forearm Glucose Uptake and Metabolism in Chronic Heart Failure

The activity of the sympathetic nervous system seems to influence the uptake (and handling) of glucose by the skeletal muscle of the forearm. Conditions in which sympathetic activity is in...

Medical and Biotech [MESH] Definitions

Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.

Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.

Compounds that specifically inhibit the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent. These agents have been used in treatment of depression, panic disorder, obsessive-compulsive behavior, and alcoholism, as analgesics, and to treat obesity and bulimia. Many of the ADRENERGIC UPTAKE INHIBITORS also inhibit serotonin uptake; they are not included here.

A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release.

Membrane transport proteins found predominately in NEURONS and neuroendocrine cells that facilitate neurotransmitter transport. They include two distinct families of proteins that transport NEUROTRANSMITTERS across the PLASMA MEMBRANE and that transport NEUROTRANSMITTERS into SECRETORY VESICLES.


Advertisement
 

Relevant Topics

Neurology - Central Nervous System (CNS)
Latest News Clinical Trials Research Drugs Reports Corporate
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinsons Sleep Disorders Neurology is the branch of medicine concer...

Alzheimer's Disease
Latest News Clinical Trials Research Drugs Reports Corporate
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Advertisement
 

Searches Linking to this Article