scholarly journals Amethystic agents influencing toxicodynamics of ethanol

2013 ◽  
Vol 59 (6) ◽  
pp. 604-621
Author(s):  
A.I. Golovko
Keyword(s):  
Arachidonic Acid ◽  
Opioid Receptors ◽  
Second Messengers ◽  
Benzodiazepine Receptors ◽  
Metabotropic Receptors ◽  
Glutamate Antagonists ◽  
Reversible Inhibitors ◽  
Neurotransmitter Systems ◽  
Selective Antagonists ◽  
Opioid Neuropeptides

The pathogenetic mechanisms of acute alcoholic intoxications are examined and is based the expediency of the search for the amethystic agents, which influence neurotransmitter systems. Promising should be considered the agents, which modulate GABA-systems (partial reverse agonists of benzodiazepine receptors), glutamate (antagonists of metabotropic receptors mGluR2/3), opioid neuropeptides (antagonists of opioid receptors), acetylcholine (reversible inhibitors of acetylcholinesterase and M-cholinoagonists), adenosine (selective antagonists of A -receptors). The amethystic effect manifest also the substances, which modify the second messengers systems (calcium, nitrergic and cascade of arachidonic acid). The most of the means examined possesses the moderate amethystic potential, and effectiveness is manifested predominantly during the preventive application.

scholarly journals A pertussis-toxin-sensitive protein controls exocytosis in chromaffin cells at a step distal to the generation of second messengers

1991 ◽  
Vol 274 (2) ◽  
pp. 339-347 ◽  
Author(s):  
J M Sontag ◽  
D Thierse ◽  
B Rouot ◽  
D Aunis ◽  
M F Bader
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
G Protein ◽  
Pertussis Toxin ◽  
Chromaffin Cells ◽  
Second Messengers ◽  
Catecholamine Release ◽  
Secretory Process ◽  
Permeabilized Cells ◽  
Arachidonic Acid Concentration

The role of GTP-binding proteins (G-proteins) in the secretory process in chromaffin cells was investigated by studying the effects of pertussis toxin (PTX) on catecholamine release and generation of various second messengers. PTX was found to stimulate the catecholamine secretion induced by nicotine, 59 mM-K+ or veratridine. PTX also potentiated Ca2(+)-evoked catecholamine release from permeabilized chromaffin cells, suggesting that PTX substrate(s) regulate the exocytotic machinery at a step distal to the rise in intracellular Ca2+. We have investigated the possible intracellular pathways involved in the stimulation of secretion by PTX. PTX did not modify the translocation of protein kinase C (PKC) to membranes in intact or permeabilized cells; in addition, neither inhibitors nor activators of PKC had any effect on catecholamine release induced by PTX. Thus it seems unlikely that the effect of PTX on secretion is mediated by activation of PKC. The effect of PTX is also cyclic AMP-independent, as PTX did not change cytoplasmic cyclic AMP levels. The relationship between PTX treatment and arachidonic acid release was also examined. We found that an increase in cytoplasmic arachidonic acid concentration enhanced Ca2(+)-evoked catecholamine release in permeabilized cells, but arachidonic acid did not mimic the effect of PTX on the Ca2(+)-dose-response curve for secretion. Furthermore, PTX did not significantly modify the release of arachidonic acid measured in resting or stimulated chromaffin cells, suggesting that the stimulatory effect of PTX on secretion is not mediated by an activation of phospholipase A2. Taken together, these results suggest that PTX may modulate the intracellular machinery of secretion at a step distal to the generation of second messengers. In alpha-toxin-permeabilized cells, full retention of the PTX-induced activation of secretion was observed even 30 min after permeabilization. In contrast, when chromaffin cells were permeabilized with streptolysin-O (SLO), there was a marked progressive loss of the PTX effect. We found that SLO caused the rapid leakage of three G-protein alpha-subunits which are specifically ADP-ribosylated by PTX. We propose that a PTX-sensitive G-protein may play an inhibitory role in the final stages of the Ca2(+)-evoked secretory process in chromaffin cells.

scholarly journals Molecular control of luteal secretion of progesterone

Reproduction ◽  
2002 ◽  
pp. 333-339 ◽  
Author(s):  
GD Niswender
Keyword(s):  
Mitochondrial Membrane ◽  
Smooth Endoplasmic Reticulum ◽  
Second Messengers ◽  
Benzodiazepine Receptors ◽  
Regulatory Protein ◽  
Density Lipoprotein ◽  
Cholesterol Transport ◽  
Inner Mitochondrial Membrane ◽  
Molecular Control ◽  
Natural Ligand

Cholesterol provided by low- or high-density lipoprotein is the precursor for biosynthesis of progesterone. Once inside the cell, cholesterol can be used for steroidogenesis or esterified with long-chain fatty acids and stored as cholesterol esters in lipid droplets. When it is needed for steroidogenesis, free cholesterol is transported to the mitochondrion via a mechanism that involves cytoskeletal elements and sterol carrier proteins. Cytochrome P450 cholesterol side chain cleavage enzyme complex converts the cholesterol to pregnenolone, which is then converted to progesterone by 3beta-hydroxysteroid dehydrogenase/delta5,delta4 isomerase in the smooth endoplasmic reticulum. Transport of cholesterol from the cytoplasm to the inner mitochondrial membrane is both the rate-limiting step in progesterone biosynthesis and the step most acutely influenced by second messengers. Steroidogenic acute regulatory protein (StAR) and peripheral-type benzodiazepine receptors (PBR) are involved in this transport. StAR may bind cholesterol in the cytosol and transport it to the mitochondrial membrane where PBR is involved in transport from the outer to the inner mitochondrial membrane. Phosphorylation of StAR by protein kinase A (PKA) stimulates cholesterol transport, whereas phosphorylation by PKC may inhibit this process. Endozepine, the natural ligand for PBR, also appears to be involved in regulation of the rate of cholesterol transport to the inner mitochondrial membrane and to play a role in the stimulatory effects of PKA on steroidogenesis. Increased concentrations of endozepine were detected in large luteal cells, and may explain the increased progesterone secretion from this type of cell. Fluorescence energy transfer procedures indicate that StAR associates with PBR in mitochondrial membranes. A model is presented for the proposed interactions of StAR, PBR and endozepine in the transport of cholesterol from the outer to the inner mitochondrial membrane.

Arachidonic acid inhibits potassium conductances in cultured rat oligodendrocytes

1995 ◽  
Vol 269 (2) ◽  
pp. C341-C348 ◽  
Author(s):  
B. Soliven ◽  
N. Wang
Keyword(s):  
Arachidonic Acid ◽  
Second Messengers ◽  
Membrane Depolarization ◽  
Patch Clamp Technique ◽  
Metabolic Products ◽  
Potassium Conductances ◽  
K Current ◽  
Intracellular Second Messengers ◽  
Inwardly Rectifying ◽  
K Currents

Arachidonic acid (AA) and its metabolites play a dual role as intracellular second messengers and as transcellular mediators of neural activity. We have previously shown that AA increases cytosolic Ca2+ in oligodendrocytes. In this work, we studied the effects of AA and other fatty acids on whole cell K+ currents of cultured rat oligodendrocytes using the patch-clamp technique. We found that 1) AA decreased the current amplitudes of both the inwardly rectifying K+ current (IKir) and the outward K+ currents (IKo) resulting in membrane depolarization; 2) AA also induced IKo current inactivation/blocked state; 3) AA appeared to act directly on K+ channels and not indirectly via its metabolic products, activation of protein kinase C, or by generation of oxygen free radicals. We have thus demonstrated an additional mechanism for AA-induced signaling in oligodendrocytes, i.e., via modulation of K+ conductances leading to membrane depolarization. The latter has been shown to influence protein phosphorylation and perhaps other important functional output of oligodendrocytes.

scholarly journals An opioid-like system regulating feeding behavior in C. elegans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mi Cheong Cheong ◽  
Alexander B Artyukhin ◽  
Young-Jai You ◽  
Leon Avery
Keyword(s):  
Caenorhabditis Elegans ◽  
Feeding Behavior ◽  
Opioid Receptors ◽  
Motor Neurons ◽  
Sequence Similarity ◽  
Rnai Screen ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
C Elegans ◽  
Opioid Neuropeptides

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggest C. elegans may be the first genetically tractable invertebrate opioid model.

scholarly journals Regulation of macrophage eicosanoid production by hydroperoxy-and hydroxy-eicosatetraenoic acids

1986 ◽  
Vol 233 (1) ◽  
pp. 199-206 ◽  
Author(s):  
J L Humes ◽  
E E Opas ◽  
M Galavage ◽  
D Soderman ◽  
R J Bonney
Keyword(s):  
Cell Culture ◽  
Arachidonic Acid ◽  
Peritoneal Macrophages ◽  
Lipoxygenase Pathway ◽  
Reversible Inhibitors ◽  
Irreversible Inhibitors ◽  
Intracellular Regulation ◽  
Macrophage Populations ◽  
Mouse Peritoneal Macrophages ◽  
Hydroxyeicosatetraenoic Acids

Resident mouse peritoneal macrophages when exposed to zymosan during the first day of cell culture synthesize and secrete large amounts of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), the respective products of cyclo-oxygenase- and 5-lipoxygenase-catalysed oxygenations of arachidonic acid. Under these conditions of cell stimulation only small amounts of hydroxyeicosatetraenoic acids (HETEs) are concomitantly produced. However, exogenously added arachidonic acid is metabolized to large amounts of 12- and 15-HETE and only relatively small amounts of PGE2. No LTC4 is formed under these conditions. In contrast, resident mouse peritoneal macrophages in cell culture for 4 days synthesized less PGE2 and LTC4 when exposed to zymosan. However, these macrophage populations continue to synthesize 12-HETE from exogenously added arachidonic acid. Zymosan induced the secretion of a lysosomal enzyme, N-acetyl-beta-glucosaminidase, equally in both 1- and 4-day cultures. Both 12- and 15-hydroperoxyeicosatetraenoic acids (HPETEs), the precursors of 12- and 15-HETE, were found to be irreversible inhibitors of the cyclo-oxygenase pathway and reversible inhibitors of the 5-lipoxygenase pathway in macrophages. 15-HETE were found to be reversible inhibitors of both pathways. Thus the oxidation of arachidonic oxidation of arachidonic acid to both prostaglandins and leukotrienes may be under intracellular regulation by products of 12- and 15-lipoxygenases.

Cholinergic and Glutaminergic Excitation of Neuronal Cells

1996 ◽  
Vol 24 (3) ◽  
pp. 387-392
Author(s):  
Kai M. Savolainen ◽  
Pirkko Tervo ◽  
Jarkko Loikkanen ◽  
Jonne Naarala
Keyword(s):  
Intracellular Calcium ◽  
Muscarinic Receptors ◽  
Oxidative Burst ◽  
Neuronal Damage ◽  
Second Messengers ◽  
Neuronal Cells ◽  
Salient Feature ◽  
Receptor Activation ◽  
Metabotropic Receptors ◽  
Free Intracellular Calcium

Excessive cholinergic or glutaminergic brain stimulation may result in seizures, excitotoxicity and neuronal damage. Cholinergic neuronal excitation is mediated via muscarinic receptors which couple with GTP-binding proteins (G–proteins), activate phospholipase C, and produce the inositol lipid second messengers, inositol-1,4,5,-trisphosphate (InsP3) and diacyl-glycerol (DG). InsP3 facilitates intracellular Ca2+ metabolism and DG activates protein kinase C (PKC). Glutaminergic neuronal stimulation is mediated through ionotropic N-methyl-D-aspartate (NMDA) receptors, which increase Ca2+ influx, and kainate α-amino-3-hydroxy-5-methyl-4-isoxalolproprionic acid receptors, which mainly regulate Na+ fluxes. Glutaminergic metabotropic receptors are also coupled to a G-protein, and their stimulation activates neurons through increased production of InsP3 and DG. A salient feature in glutamate-induced excitotoxicity is the induction of an oxidative burst, subsequent oxidative stress, and damage to the neurons. The glutamate-induced oxidative burst can be amplified by lead, a direct activator of PKC, and the oxidative burst can be blocked by a PKC inhibitor, suggesting an important role for PKC. Carbachol also induces an oxidative burst in neuronal cells and this is associated with elevations of free intracellular calcium. The ability of an NMDA receptor antagonist, AP-5, to block carbachol-induced elevations of free intracellular calcium, suggests that activation of muscarinic receptors is associated with a simultaneous glutamate receptor activation. Thus, cross-talk between cholinergic muscarinic and glutaminergic receptors may be an important contributing factor in cholinergic and glutaminergic excitotoxicity.

scholarly journals Correspondence between gene expression and neurotransmitter receptor and transporter density in the human brain

2021 ◽  
Author(s):  
Justine Y Hansen ◽  
Ross D Markello ◽  
Lauri Tuominen ◽  
Martin Norgaard ◽  
Elena Kuzmin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Present Report ◽  
Neurotransmitter Receptors ◽  
Metabotropic Receptors ◽  
Microarray Gene Expression ◽  
Neurotransmitter Receptor ◽  
Neurotransmitter Systems ◽  
Brain Structure And Function ◽  
And Function ◽  
Direct Measures

Neurotransmitter receptors modulate the signaling between neurons. Thus, neurotransmitter receptors and transporters play a key role in shaping brain function. Due to the lack of comprehensive neurotransmitter receptor/transporter density datasets, microarray gene expression is often used as a proxy for receptor densities. In the present report, we comprehensively test the expression-density association for a total of 27 neurotransmitter receptors, receptor binding-sites, and transporters across 9 different neurotransmitter systems, using both PET and autoradiography imaging modalities. We find poor spatial correspondences between gene expression and density for all neurotransmitter receptors and transporters except four single-protein metabotropic receptors (5-HT1A, D2, CB1, and MOR). These expression-density associations are related to population variance and change across different classes of laminar differentiation. Altogether, we recommend using direct measures of receptor and transporter density when relating neurotransmitter systems to brain structure and function.

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