σ Receptors: Historical Perspective and Background

Matsumoto, Rae R.

doi:10.1007/978-0-387-36514-5_1

Cited by 31 publications

(45 citation statements)

References 108 publications

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“…Together, it is likely that the action of s1R on VGCCs results in an overall decrease of Ca 21 influx. Why high doses ($100 mM) of s1R agonists are required on voltage-gated ion channel (Church and Fletcher, 1995;Lupardus et al, 2000;Zhang and Cuevas, 2002) compared with its high receptor affinity (McCann et al, 1994;Matsumoto, 2007;Su et al, 2010) is not clearly understood. This could be due to the influence of the cellular environment, such as s1R-binding partners, post-translational modifications, isoform variations in s1R (Shioda et al, 2012), or direct interaction with the VGCC independent of the s1R high-affinity binding site (Church and Fletcher, 1995;Tchedre et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…After activation, s1R traffics to various subcellular compartments, including the plasmalemma, and regulates diverse functions (Su et al, 2010). The s1R is found in a range of tissues, including the central nervous system (Alonso et al, 2000;Matsumoto, 2007), where s1R modulation of neuronal ion channels and activity is associated with neurologic and psychiatric conditions (Kourrich et al, 2012). We have recently demonstrated that s1R is also present in the peripheral nervous system, in both sensory neurons and satellite glial cells of the dorsal root ganglion (DRG) (Bangaru et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons

Pan

Guo

Kwok

et al. 2014

J Pharmacol Exp Ther

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Sigma-1 receptor (s1R), an endoplasmic reticulum-chaperone protein, can modulate painful response after peripheral nerve injury. We have demonstrated that voltage-gated calcium current is inhibited in axotomized sensory neurons. We examined whether s1R contributes to the sensory dysfunction of voltagegated calcium channel (VGCC) after peripheral nerve injury through electrophysiological approach in dissociated rat dorsal root ganglion (DRG) neurons. Animals received either skin incision (Control) or spinal nerve ligation (SNL). Both s1R agonists, (1)pentazocine (PTZ) and DTG [1,3-di-(2-tolyl)guanidine], dose dependently inhibited calcium current (I Ca ) with Ba 21 as charge carrier in control sensory neurons. The inhibitory effect of s1R agonists on I Ca was blocked by s1R antagonist, BD1063(1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine dihydrochloride) or BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide). PTZ and DTG showed similar effect on I Ca in axotomized fifth DRG neurons (SNL L5). Both PTZ and DTG shifted the voltage-dependent activation and steady-state inactivation of VGCC to the left and accelerated VGCC inactivation rate in both Control and axotomized L5 SNL DRG neurons. The s1R antagonist, BD1063 (10 mM), increases I Ca in SNL L5 neurons but had no effect on Control and noninjured fourth lumbar neurons in SNL rats. Together, the findings suggest that activation of sR1 decreases I Ca in sensory neurons and may play a pivotal role in pain generation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons

Pan

Guo

Kwok

et al. 2014

J Pharmacol Exp Ther

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“…In contrast, less is known about 2 receptors. They are slightly smaller than 1 receptors and have not been cloned (Matsumoto, 2007a). Although truly selective 2 compounds are not yet available, they are under development (Mésangeau et al, 2008).…”

Section: Abbreviationsmentioning

confidence: 99%

“…Although antagonists of receptors have been synthesized and evaluated using both in vitro and in vivo methods, a major drawback is that many of them are not purely -selective (Matsumoto, 2007;Newman and Coop, 2007). Besides receptors, many compounds also bind to dopamine transporters, opioid receptors, or N-methyl-Daspartate (NMDA) receptors (Matsumoto, 2007a). Studies using nonselective compounds can confound the interpretation of the role of receptors and lead to confusing phenomena in behavioral tests.…”

Section: Abbreviationsmentioning

confidence: 99%

A Novel Substituted Piperazine, CM156, Attenuates the Stimulant and Toxic Effects of Cocaine in Mice

Xu¹,

Kaushal²,

Shaikh³

et al. 2010

J Pharmacol Exp Ther

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Cocaine is a highly abused drug without effective pharmacotherapies to treat it. It interacts with sigma () receptors, providing logical targets for the development of medications to counteract its actions. Cocaine causes toxic and stimulant effects that can be categorized as acute effects such as convulsions and locomotor hyperactivity and subchronic effects including sensitization and place conditioning. In the present study, 3-(4-(4-cyclohexylpiperazin-1-yl)butyl)benzo[d]thiazole-2(3H)-thione (CM156), a novel compound, was developed and tested for interactions with receptors using radioligand binding studies. It was also evaluated against cocaine-induced effects in behavioral studies. The results showed that CM156 has nanomolar affinities for each of the receptor subtypes in the brain and much weaker affinities for non-binding sites. Pretreatment of male Swiss-Webster mice with CM156, before administering either a convulsive or locomotor stimulant dose of cocaine, led to a significant attenuation of these acute effects. CM156 also significantly reduced the expression of behavioral sensitization and place conditioning evoked by subchronic exposure to cocaine. The protective effects of CM156 are consistent with receptor-mediated actions. Together with previously reported findings, the data from CM156 and related compounds indicate that receptors can be targeted to alleviate deleterious actions of cocaine.

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“…[15][16][17] Second, ligand binding and photoaffinity labeling studies have demonstrated a lower expression of sigma-2 versus sigma-1 receptors in normal tissues from the central nervous system, gastrointestinal tract, kidney, liver, and heart. 18 Third, a correlation between sigma-2 receptor expression and tumor proliferation has been established both in vitro and in vivo, 19,20 but no such correlation was observed for the sigma-1 subtype.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of a selective sigma-2 receptor ligand enhances uptake of liposomes by multiple cancer cells

Zhang¹,

Huang²,

Zhang³

et al. 2012

IJN

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Background:The sigma-2 receptor is an attractive target for tumor imaging and targeted therapy because it is overexpressed in multiple types of solid tumors, including prostate cancer, breast cancer, and lung cancer. SV119 is a synthetic small molecule that binds to sigma-2 receptors with high affinity and specificity. This study investigates the utility of SV119 in mediating the selective targeting of liposomal vectors in various types of cancer cells. Methods: SV119 was covalently linked with polyethylene glycol-dioleyl amido aspartic acid conjugate (PEG-DOA) to generate a novel functional lipid, SV119-PEG-DOA. This lipid was utilized for the preparation of targeted liposomes to enhance their uptake by cancer cells. Liposomes with various SV119 densities (0, 1, 3, and 5 mole%) were prepared and their cellular uptake was investigated in several tumor cell lines. In addition, doxorubicin (DOX) was loaded into the targeted and unmodified liposomes, and the cytotoxic effect on the DU-145 cells was evaluated by MTT assay. Results: Liposomes with or without SV119-PEG-DOA both have a mean diameter of approximately 90 nm and a neutral charge. The incorporation of SV119-PEG-DOA significantly increased the cellular uptake of liposomes by the DU-145, PC-3, A549, 201T, and MCF-7 tumor cells, which was shown by fluorescence microscopy and the quantitative measurement of fluorescence intensity. In contrast, the incorporation of SV119 did not increase the uptake of liposomes by the normal BEAS-2B cells. In a time course study, the uptake of SV119 liposomes by DU-145 cells was also significantly higher at each time point compared to the unmodified liposomes. Furthermore, the DOX-loaded SV119 liposomes showed significantly higher cytotoxicity to DU-145 cells compared to the DOX-loaded unmodified liposomes. Conclusion: SV119 liposomes were developed for targeted drug delivery to cancer cells. The targeting efficiency and specificity of SV119 liposomes to cancer cells was demonstrated in vitro. The results of this study suggest that SV119-modified liposomes might be a promising drug carrier for tumor-targeted delivery.

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σ Receptors: Historical Perspective and Background

Cited by 31 publications

References 108 publications

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons

A Novel Substituted Piperazine, CM156, Attenuates the Stimulant and Toxic Effects of Cocaine in Mice

Incorporation of a selective sigma-2 receptor ligand enhances uptake of liposomes by multiple cancer cells

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σ Receptors: Historical Perspective and Background

Cited by 31 publications

References 108 publications

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca2+ Current in Sensory Neurons

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca2+ Current in Sensory Neurons

A Novel Substituted Piperazine, CM156, Attenuates the Stimulant and Toxic Effects of Cocaine in Mice

Incorporation of a selective sigma-2 receptor ligand enhances uptake of liposomes by multiple cancer cells

Contact Info

Product

Resources

About

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons