Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role the Na/Ca-exchange and intracellular Ca2+ released from Ca(2+)-depots in the modulatory action of Na,K-pump inhibitor ouabain on cholinosensitivity in the command neurons of Helix lucorum was studied in a cellular analogue of habituation. The integral transmembrane inward currents in LPa2, LPa3, RPa3, and RPa2 neurons were recorded in Helix lucorum ganglia preparation using two-electrode voltage clamp technique. The reduction of cholinosensitivity of a neuron was estimated as a depth of the depression of the acetylcholine-induced inward currents during the rhythmic local acetylcholine applications (with the interstimulus interval of 2-4 min) on a somatic membrane. The inhibitor of the Na/Ca-exchange benzamil (the extracellular action, 15-35 mcM) and two specific inhibitors of Ca-ATPase in the sarcoplasmic and endoplasmic reticulum, cyclopiazonic acid and thapsigargin (intracellular injection by spontaneous diffusion, 0.1 mM) prevented the modification of the depression of acetylcholine-induced current by ouabain (100 mcM) during the rhythmic application of acetylcholine. A conclusion is drawn that the inhibitor of the Na,K-pump ouabain modifies the depression of neuron cholinosensitivity in the cellular analogue of habituation via the Na/Ca-exchange and intracellular Ca2+ released from Ca2+ depots.
 ...
PMID:[Participation of Na/Ca-exchange and intracellular mobilized Ca2+ in regulating depression of cholino-sensitive Helix lucorum neurons to a cellular analog of habituation]. 1187 Oct 37

The role of Na/Ca exchange and intracellular mobilized Ca2+ in modifying the depression of defensive behavior command neuron cholinosensitivity induced by the the Na,K pump inhibitor ouabain was studied in common snails using a cellular analog of habituation. Integral transmembrane acetylcholine-evoked currents (ACh currents) were recorded using a two-electrode membrane potential clamping technique. Decreases in neuron cholinosensitivity in the cellular analog of habituation were assessed in terms of the depth of depression of the amplitude of ACh currents during rhythmic local application of acetylcholine (with interstimulus intervals of 2-4 min) to the somatic membrane. The Na/Ca exchange inhibitor benzamyl (applied extracellularly, 15-35 microM) and two specific endoplasmic reticulum Ca-ATPase inhibitors, cyclopiazonic acid and thapsigargin (applied intracellularly. 0.1 mM) prevented modification of depression of the ACh current by ouabain (100 microM). It is concluded that Na/Ca exchange and the release of mobilized Ca2+ from intracellular calcium depots are involved in the mechanism by which the Na,K pump controls the depression of neuron cholinosensitivity in the cellular analog of habituation.
 ...
PMID:Involvement of Na/Ca exchange and intracellular mobilized Ca2+ in Na,K-pump-mediated control of depression of the cholinosensitivy of common snail neurons [correction of neorons] using a cellular analog of habituation. 1266 81

The brain sigma-1 receptors can bind neurosteroids and psychotropic drugs, including neuroleptics and cocaine and are implicated in schizophrenia, depression, and drug dependence. In this study, we found that sigma-1 receptors specifically target lipid storage sites (lipid droplets) on the endoplasmic reticulum by forming a distinct class of lipid microdomains. Both endogenously expressing sigma-1 receptors and transfected C-terminally enhanced yellow fluorescent protein (EYFP)-tagged sigma-1 receptors (Sig-1R-EYFP) target unique "ring-like" structures associated with endoplasmic reticulum reticular networks in NG108-15 cells. The ring-like structures contain neutral lipids and are enlarged by the oleate treatment, indicating that they are endoplasmic reticulum-associated lipid droplets (ER-LDs). sigma-1 receptors colocalize with caveolin-2, a cholesterol-binding protein in lipid rafts on the ER-LDs, but not with adipocyte differentiation-related protein (ADRP), a cytosolic lipid droplet (c-LD)-specific protein. When the double-arginine ER retention signal on the N terminus of sigma-1 receptors is truncated, sigma-1 receptors no longer exist on ER-LDs, but predominantly target c-LDs, which contain ADRP. sigma-1 receptors on ER-LDs form detergent-resistant raft-like lipid microdomains, the buoyancy of which is different from that of plasma membrane lipid rafts. (+)-Pentazocine causes sigma-1 receptors to disappear from the microdomains. N-Terminally EYFP-tagged sigma-1 receptors (EYFP-Sig-1R) failed to target ER-LDs. EYFP-Sig-1R-transfected cells showed an unrestricted distribution of neutral lipids all over the endoplasmic reticulum network, decreases in c-LDs and cholesterol in plasma membranes, and the bulbous aggregation of endoplasmic reticulum. Thus, sigma-1 receptors are unique endoplasmic reticulum proteins that regulate the compartmentalization of lipids on the endoplasmic reticulum and their export from the endoplasmic reticulum to plasma membrane and c-LDs.
 ...
PMID:Sigma-1 receptors (sigma(1) binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: roles in endoplasmic reticulum lipid compartmentalization and export. 1273 Mar 55

Although sigma receptors were discovered in 1982, the biochemical and physiological roles of sigma receptors have just begun to unveil. Sigma receptors are non-opioid, non-phencyclidine receptors that contain two subtypes: sigma-1 and sigma-2 receptors. The sigma-1 receptor has been cloned and its sequence does not resemble that of any mammalian protein. Sigma-2 receptors have not been cloned. The focus of this review will be on sigma-1 receptors. Sigma-1 receptors contain 223 amino acids and reside primarily at the endoplasmic reticulum. Sigma-1 receptors exist mainly in the central nervous system, but also in the periphery. Sigma-1 receptor ligands include cocaine, (+)-benzomorphans like (+)-pentazocine and (+)N-allyl-normetazocine (or (+)-SKF-10047), and endogenous neurosteroids like progesterone and pregnenolone sulfate. Many pharmacological and physiological actions have been attributed to sigma-1 receptors. These include the regulation of IP3 receptors and calcium signaling at the endoplasmic reticulum, mobilization of cytoskeletal adaptor proteins, modulation of nerve growth factor-induced neurite sprouting, modulation of neurotransmitter release and neuronal firing, modulation of potassium channels as a regulatory subunit, alteration of psychostimulant-induced gene expression, and blockade of spreading depression. Behaviorally, sigma-1 receptors are involved in learning and memory, psychostimulant-induced sensitization, cocaine-induced conditioned place preference, and pain perception. Notably, in almost all the aforementioned biochemical and behavioral tests, sigma-1 agonists, while having no effects by themselves, caused the amplification of signal transductions incurred upon the stimulation of the glutamatergic, dopaminergic, IP3-related metabotropic, or nerve growth factor-related systems. Thus, it is hypothesized that sigma-1 receptors, at least in part, are intracellular amplifiers creating a supersensitized state for signal transduction in the biological system.
 ...
PMID:Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction. 1287 Oct 86

Preconditioning is a process where a preceding non-lethal form of stress activates a stress response that protects cells against an otherwise lethal form of stress. Preconditioning can be induced in various ways including short-term ischemia or spreading depression. Here we investigated the effect of 1 h repetitive spreading depression on the unfolded protein response (UPR), a stress response activated under conditions associated with endoplasmic reticulum (ER) dysfunction. Spreading depression induced processing of xbp1 mRNA, indicative of an activation of UPR. Processing of xbp1 was paralleled by a rise in grp78 mRNA levels resulting from an activation of a signal transduction pathway that depends on protein synthesis. Preconditioning-induced activation of UPR may preserve ER functioning under pathological conditions interfering with ER functions.
 ...
PMID:Spreading depression activates unfolded protein response. 1534 30

The trans-10, cis-12 CLA isomer has been causally related to milk fat depression in dairy cows, although no molecular mechanism has been established. Sterol response element-binding protein (SREBP)-1 is a transcription factor synthesized and retained as a membrane-bound precursor in the endoplasmic reticulum and proteolytically cleaved to release an active fragment that migrates to the nucleus to stimulate lipogenic gene transcription. Certain lipid molecules (i.e., PUFA) were shown to inhibit the proteolytic activation of SREBP-1 in rodent liver models, although there has been no previous demonstration of its presence in bovine tissues or in mammary tissue of any species. We used a bovine mammary cell line (MAC-T) to assess the involvement of SREBP-1 in the regulation of lipid synthesis in bovine mammary cells by trans-10, cis-12 CLA. Treatment with 75 micromol/L trans-10, cis-12 CLA for 48 h resulted in an approximately 50% reduction of (14)C-acetate incorporation into total lipid and corresponding reductions in mRNA abundance for acetyl CoA carboxylase, fatty acid synthase, and stearoyl CoA desaturase, whereas cis-9, trans-11 CLA had no effect on these genes. There was no reduction in SREBP-1 mRNA or precursor protein, but the abundance of the activated nuclear fragment of the protein was significantly reduced by treatment with 75 micromol/L trans-10, cis-12 CLA. These results indicate that trans-10, cis-12 CLA reduces lipid synthesis in the bovine mammary gland through inhibition of the proteolytic activation of SREBP-1 and subsequent reduction in transcriptional activation of lipogenic genes.
 ...
PMID:The inhibitory effect of trans-10, cis-12 CLA on lipid synthesis in bovine mammary epithelial cells involves reduced proteolytic activation of the transcription factor SREBP-1. 1546 41

The sigma(1) receptor is a 223 amino acid protein sharing no homology with other mammalian protein. It is an intracellular protein present on the endoplasmic reticulum membrane, which can translocates to other organelles and plasma membranes after activation. Activation of the sigma(1) receptor results in modulation of calcium mobilization from inositol trisphosphate receptor-gated intracellular pools and, at the plasma membrane, in modulation of several neurotransmitter responses. Behaviorally, sigma(1) receptors are involved in learning and memory, response to stress and depression, psychostimulant-induced sensitization, vulnerability to addiction and pain perception. Numerous synthetic compounds bind to sigma(1) receptor, playing the role of activator/agonist or blocker/antagonist, and these include benzomorphans, neuroleptics, antidepressants, cocaine, peptides related to neuropeptide Y or calcitonin gene-related peptide. It is also the case of neuro(active)steroids, i. e., circulating neuroactive steroids and neurosteroids synthesized de novo by the brain, which appear as the most important endogenous modulators of sigma(1) receptor. Pregnenolone and dehydroepiandrosterone act as sigma(1) receptor agonists and progesterone is a potent antagonist. The present paper will review the molecular and biochemical features concerning the sigma(1) receptor and focus on the recent studies examining the impact of the neuro(active)steroid/sigma(1) receptor interaction on the antidepressant activity of sigma(1) receptor agonists in the context of neurodegenerative diseases.
 ...
PMID:Neurosteroids and sigma1 receptors, biochemical and behavioral relevance. 1554 83

Sigma receptors were first described as one of the opiate receptor subtypes. Now it is well established that sigma receptors, existing as subtypes sigma-1 and sigma-2, are unique non-opioid receptors which are implicated in higher-ordered brain functions. Sigma-1 receptors have high to moderate affinities for (+)benzomorphans and also many psychotrophic drugs and neurosteroids. Sigma-1 receptor agonists and certain neurosteroids such as dehydroepiandrosterone sulfate (DHEA-S) have antidepressant-like effects in animal behavioral models of depression. The antidepressant-like effect induced by sigma-1 receptor agonists may involve intracellular Ca (2+) mobilization such that sigma-1 receptor agonists modulate Ca (2+) release from endoplasmic reticulum (ER) in a cytoskeletal protein-dependent manner. In addition, growth factor-induced neurite outgrowth is mediated through sigma-1 receptors, suggesting a role of antidepressants in neuroplasticity. Igmesine (JO1783), OPC-14 523 and SA4503, have recently been developed as sigma-1 agonists and are found to have antidepressant-like activity perhaps with fewer side effects. This article reviews the new potential use of sigma-1 receptor ligands in the treatment of mood disorder.
 ...
PMID:A perspective on the new mechanism of antidepressants: neuritogenesis through sigma-1 receptors. 1554 87

Familial hemiplegic migraine type 2, an autosomal dominant form of migraine with aura, has been associated with four distinct mutations in the alpha2-subunit of the Na+,K+-ATPase. We have introduced these mutations in the alpha2-subunit of the human Na+,K+-ATPase and the corresponding mutations in the Bufo marinus alpha1-subunit and studied these mutants by expression in Xenopus oocyte. Metabolic labeling studies showed that the mutants were synthesized and associated with the beta-subunit, except for the alpha2HW887R mutant, which was poorly synthesized, and the alpha1BW890R, which was partially retained in the endoplasmic reticulum. [3H]ouabain binding showed the presence of the alpha2HR689Q and alpha2HM731T at the membrane, whereas the alpha2HL764P and alpha2HW887R could not be detected. Functional studies with the mutants of the B. marinus Na+,K+-ATPase showed a reduced or abolished electrogenic activity and a low K+ affinity for the alpha1BW890R mutant. Through different mechanisms, all these mutations result in a strong decrease of the functional expression of the Na+,K+-pump. The decreased activity in alpha2 isoform of the Na+,K+-pump expressed in astrocytes seems an essential component of hemiplegic migraine pathogenesis and may be responsible for the cortical spreading depression, which is one of the first events in migraine attacks.
 ...
PMID:Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic migraine. 1597 Jun 28

The neurochemistry of feeding was a highlight of this meeting. A number of peptides are now known to participate in the control of nutrient balance, and many of them featured in the meeting, including the feeding suppressors alpha-melanocyte-stimulating hormone, leptin and corticotrophin releasing hormone, and the orexigenic agents, melanin-concentrating hormone, Agouti-related peptide, orexin A and neuropeptide Y. Other substances that play a role in feeding are amylin and its antagonist, AC-187, histamine, dopamine, serotonin, opiates, galanin and CART peptides. The hypothalamic and extrahypothalamic localization of these feedingrelated substances and their interactions with one another, and other brain regions, are beginning to be understood. Another symposium focused on sigma receptor ligands, such as (+)-pentazocine, PRE-084, the neurosteroid pregnanolone sulfate, NE-100, igmesine (JO-1784) and BD-1008 and related compounds. Results showed that sigma ligands may affect Ca(2+) signaling via two modes of action, one being at the endoplasmic reticulum and the other at the plasma membrane. Sigma receptors have been implicated in learning and memory, and may play a role in anxiety and depression.
 ...
PMID:International Behavioral Neuroscience Society - Ninth meeting. Neurochemistry of feeding. 1608 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>