Sigma-1 Receptor Regulation of Voltage-Gated Calcium Channels Involves a Direct Interaction

Tchedre, Kissaou; Huang, Ren-Qi; Dibas, Adnan; Krishnamoorthy, Raghu R; Dillon, Glenn H.; Yorio, Thomas

doi:10.1167/iovs.08-1867

Cited by 118 publications

(88 citation statements)

References 44 publications

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“…We focused on SOCE, but recruitment of σ1Rs to ER-PM junctions by STIM1 might also be involved in regulation of other PM channels by σ1Rs (Maurice and Su, 2009;Su et al, 2010;Kourrich et al, 2013;Pabba, 2013). For example, the L-type Ca 2+ channel is inhibited by σ1R (Tchedre et al, 2008) and by depletion of intracellular Ca 2+ stores and STIM1 (Park et al, 2010;Wang et al, 2010). We suggest that STIM1-mediated translocation of σ1R to ER-PM junctions may inhibit voltage-gated Ca 2+ entry and may also deliver σ1Rs to additional PM targets (Fig.…”

Section: Discussionmentioning

confidence: 99%

Sigma1 receptors inhibit store-operated Ca²⁺ entry by attenuating coupling of STIM1 to Orai1

Srivats¹,

Balasuriya²,

Pasche³

et al. 2016

J Gen Physiol

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Section: Discussionmentioning

confidence: 99%

Sigma1 receptors inhibit store-operated Ca²⁺ entry by attenuating coupling of STIM1 to Orai1

Srivats¹,

Balasuriya²,

Pasche³

et al. 2016

J Gen Physiol

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“…LS-1-137 (10 μM) was added to the external solution and continuously perfused through the bath for 3 min. Our previous studies have shown that the onset for the effect of σ1 receptor agonist on voltage-gated calcium channels occurs at approximately 3 min (Tchedre et al, 2008). NMDAactivated currents were recorded before (control), during LS-1-137 perfusion and after washout.…”

Section: Figurementioning

confidence: 99%

The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice

Malik

Rangel‐Barajas

Sumien

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSECognitive deficits in patients with Alzheimer's disease, Parkinson's disease, traumatic brain injury and stroke often involve alterations in cholinergic signalling. Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and/or arrest the progressive loss of memory. EXPERIMENTAL APPROACHScopolamine-induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given scopolamine (1 mg·kg −1 ) were used to evaluate the ability of LS-1-137, a novel sigma (σ1) receptor-selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration. KEY RESULTSLS-1-137 is a high-affinity (Ki = 3.2 nM) σ1 receptor agonist that is 80-fold selective for σ1, compared with σ2 receptors. LS-1-137 binds with low affinity at D2-like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1-137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS-1-137 treatment was also found to trigger the release of brain-derived neurotrophic factor from rat astrocytes. CONCLUSIONS AND IMPLICATIONSThe σ1 receptor-selective compound LS-1-137 may represent a novel candidate cognitive enhancer for the treatment of muscarinic receptor-dependent cognitive deficits. AbbreviationsAD, Alzheimer's disease; BDNF, brain-derived neurotrophic factor; BiP, binding immunoglobulin protein; ER, endoplasmic reticulum; PPCC, methyl(1R,2S/1S,2R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopro-panecarboxylate; QNB, quinuclidinyl benzylate IntroductionImpairment in learning and memory is seen in (i) aged populations, (ii) patients with neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease, (iii) stroke patients and (iv) patients with traumatic brain injury (Scarpini et al., 2003;Tarawneh and Galvin, 2010;Ruscher et al., 2011). Although the causes of cognitive impairments vary, previous studies have suggested that alteration in cholinergic neurotransmission may play an important role in the disruption of learning and memory (Francis et al., 1999;Craig et al., 2011;Dumas and Newhouse, 2011). According to the cholinergic hypothesis, age-dependent cognitive decline is primarily related to impairment in cholinergic neurotransmission (Bartus et al., 1982;Coyle et al., 1983;Kirk et al., 1994). Administration of the competitive cholinergic muscarinic receptor antagonist scopolamine causes cognitive dysfunctions similar to those observed in normal aging and AD (Ebert and Kirch, 1998;Bejar et al., 1999;Klinkenberg and Blokland, 2010). A scopolamine-dependent model of cognitive deficits has been used to screen for potential cognition-enhancing drugs (Flood and Cherkin, 1986;Ennaceur and Meliani, 1992;Antonini et al., 2009;Klinkenberg and Blokland, 2010). Since the sigma σ1 receptor is known to potently modulate cho...

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“…The S1R is a ligand-regulated non-ATP-binding membrane bound chaperone protein (Hayashi and Su, 2007). In its 125 multitasking functions, the S1R has been demonstrated to physically interact with client proteins in a functional manner including ion channels such as inositol triphosphate (IP 3 ) receptors (Hayashi and Su, 2001;Wu and Bowen, 2008), voltage-gated potassium (Aydar et al, 2002), sodium (Balasuriya et al, 2012), and calcium channels (Tchedre et al, 2008), calcium-activated chloride channels (Zhang and Cuevas, 2002), and N-methyl-D-aspartate receptors (Sircar et al, 1986b;Monnet et al, 1990;Balasuriya et al, 2013;Pabba et al, 2014). Specific interactions of the S1R with several types of G-protein coupled receptors (GPCRs) (Kim et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Biochemical Pharmacology of the Sigma-1 Receptor

2015

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The sigma-1 receptor (S1R) is a 223 amino acid two transmembrane (TM) pass protein. It is a non-ATP-binding nonglycosylated ligand-regulated molecular chaperone of unknown three-dimensional structure. The S1R is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes with broad functions that regulate cellular calcium homeostasis and reduce oxidative stress. Several multitasking functions of the S1R are underwritten by chaperone-mediated direct (and indirect) interactions with ion channels, G-protein coupled receptors and cell-signaling molecules involved in the regulation of cell growth. The S1R is a promising drug target for the treatment of several neurodegenerative diseases related to cellular stress. In vitro and in vivo functional and molecular characteristics of the S1R and its interactions with endogenous and synthetic small molecules have been discovered by the use of pharmacologic, biochemical, biophysical, and molecular biology approaches. The S1R exists in monomer, dimer, tetramer, hexamer/octamer, and higher oligomeric forms that may be important determinants in defining the pharmacology and mechanism(s) of action of the S1R. A canonical GXXXG in putative TM2 is important for S1R oligomerization. The ligand-binding regions of S1R have been identified and include portions of TM2 and the TM proximal regions of the C terminus. Some client protein chaperone functions and interactions with the cochaperone 78-kDa glucose-regulated protein (binding immunoglobulin protein) involve the C terminus. Based on its biochemical features and mechanisms of chaperone action the possibility that the S1R is a member of the small heat shock protein family is discussed.

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Sigma-1 Receptor Regulation of Voltage-Gated Calcium Channels Involves a Direct Interaction

Cited by 118 publications

References 44 publications

Sigma1 receptors inhibit store-operated Ca²⁺ entry by attenuating coupling of STIM1 to Orai1

Sigma1 receptors inhibit store-operated Ca²⁺ entry by attenuating coupling of STIM1 to Orai1

The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice

Biochemical Pharmacology of the Sigma-1 Receptor

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Sigma-1 Receptor Regulation of Voltage-Gated Calcium Channels Involves a Direct Interaction

Cited by 118 publications

References 44 publications

Sigma1 receptors inhibit store-operated Ca2+ entry by attenuating coupling of STIM1 to Orai1

Sigma1 receptors inhibit store-operated Ca2+ entry by attenuating coupling of STIM1 to Orai1

The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice

Biochemical Pharmacology of the Sigma-1 Receptor

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Sigma1 receptors inhibit store-operated Ca²⁺ entry by attenuating coupling of STIM1 to Orai1

Sigma1 receptors inhibit store-operated Ca²⁺ entry by attenuating coupling of STIM1 to Orai1