Regulating ankyrin dynamics: Roles of sigma-1 receptors

Hayashi, Teruo; Su, Tsung‐Ping

doi:10.1073/pnas.98.2.491

Cited by 256 publications

(118 citation statements)

References 35 publications

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“…We demonstrated that σ1Rs were present in both sensory neurons and SGCs. In line with previous reports [5,43,53,54], we found that σ1Rs are dispersed throughout the cytoplasm of DRG neurons in all size and histochemical subgroups. Expression of the σ1R protein decreases in both axotomized L5 neurons as well as neighboring L4 neurons, and this decrease occurred in all neuronal subpopulations.…”

Section: Discussionsupporting

confidence: 93%

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Sigma-1 Receptor Expression in Sensory Neurons and the Effect of Painful Peripheral Nerve Injury

et al. 2013

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BackgroundThe sigma-1 receptor (σ1R), an endoplasmic reticulum chaperone protein, is widely distributed and regulates numerous intracellular processes in neurons. Nerve injury alters the structure and function of axotomized dorsal root ganglion (DRG) neurons, contributing to the development of pain. The σ1R is enriched in the spinal cord and modulates pain after peripheral nerve injury. However, σ1R expression in the DRG has not been studied. We therefore characterized σ1R expression in DRGs at baseline and following spinal nerve ligation (SNL) in rats.ResultsImmunohistochemical (IHC) studies in DRG sections show σ1R in both neuronal somata and satellite glial cells. The punctate distribution of σ1R in the neuronal cytoplasm suggests expression in the endoplasmic reticulum. When classified by neuronal size, large neurons (>1300 μm) showed higher levels of σ1R staining than other groups (700-1300 μm, <700 μm). Comparing σ1R expression in neuronal groups characterized by expression of calcitonin gene-related peptide (CGRP), isolectin-B4 (IB4) and neurofilament-200 (NF-200), we found σ1R expression in all three neuronal subpopulations, with highest levels of σ1R expression in the NF-200 group. After SNL, lysates from L5 DRGs that contains axotomized neurons showed decreased σ1R protein but unaffected transcript level, compared with Control DRGs. IHC images also showed decreased σ1R protein expression, in SNL L5 DRGs, and to a lesser extent in the neighboring SNL L4 DRGs. Neurons labeled by CGRP and NF-200 showed decreased σ1R expression in L5 and, to a lesser extent, L4 DRGs. In IB4-labeled neurons, σ1R expression decreased only in axotomized L5 DRGs. Satellite cells also showed decreased σ1R expression in L5 DRGs after SNL.ConclusionsOur data show that σ1R is present in both sensory neurons and satellite cells in rat DRGs. Expression of σ1R is down-regulated in axotomized neurons as well as in their accompanying satellite glial cells, while neighboring uninjured neurons show a lesser down-regulation. Therefore, elevated σ1R expression in neuropathic pain is not an explanation for pain relief after σ1R blockade. This implies that increased levels of endogenous σ1R agonists may play a role, and diminished neuroprotection from loss of glial σ1R may be a contributing factor.

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Section: Discussionsupporting

confidence: 93%

“…Fluorescent images of σ1R staining in DRG sections revealed the presence of σ1R in neuronal somata in a punctate distribution in the cytoplasm (Figure 1A,B), consistent with its location in the ER [1,43]. Double staining for σ1R combined with NeuN, a neuron-specific marker, revealed expression of σ1R in all neurons (Figure 1A).…”

Section: Resultssupporting

confidence: 60%

Sigma-1 Receptor Expression in Sensory Neurons and the Effect of Painful Peripheral Nerve Injury

et al. 2013

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“…In the ER, σ 1 agonists administered in neural cell lines caused a rise in Ca +2 flux through the IP3 receptor (IP3R) even in the presence of an IP3R inhibitor. (40) Sigma-1 receptors have also been shown to regulate the interorganelle Ca +2 signaling between the mitochondria and the ER. (37) Agonist-stimulated sigma receptors can also leave the endoplasmic reticulum and translocate to the cell membrane to inhibit the function of cell-surface ion channels.…”

Section: Effects Of Cocaine Use On the Central Nervous Systemmentioning

confidence: 99%

Systems-level view of cocaine addiction: The interconnection of the immune and nervous systems

Marasco

Goodwin

Winder

et al. 2014

Exp Biol Med (Maywood)

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The human body is a complex assembly of physiological systems designed to manage the multidirectional transport of both information and nutrients. An intricate interplay between the nervous, circulatory, and secretory systems is therefore necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and eliminate metabolic waste products and toxins. These systems also provide vulnerable routes for modification by substances of abuse. Addictive substances are, by definition, neurologically active, but as they and their metabolites are spread throughout the body via both the nervous, circulatory, respiratory and digestive systems, there is abundant opportunity for interaction with numerous cell and tissue types. Cocaine is one such substance that exerts a broad physiological effect. While a great deal of the research concerning addiction has addressed the neurological effects of cocaine use, only a few studies have been aimed at delineating the role that cocaine plays in various body systems. In this paper, we probe the current research regarding cocaine and the immune system, and map a systems-level view to outline a broader perspective of the biological response to cocaine. Specifically, our overview of the neurological and immunomodulatory effects of the drug will allow a broader perspective of the biological response to cocaine. The focus of this review is on the connection between the nervous and immune systems and the role this connection plays in the long-term complications of cocaine use. By describing the multiplicity of these connections, we hope to inspire detailed investigations into the immunological interplay in cocaine addiction.

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“…The s-1 receptor chiefly functions in a modulatory role on dopamine, acetylcholine, NMDA and opioid receptors [18]. They are understood to translocate during signaling and are linked to the modulation or production of various intracellular second messengers [9,19].…”

Section: Sigma-1 Receptorsmentioning

confidence: 99%

Early Development of Sigma-Receptor Ligands

et al. 2010

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Sigma receptors (σ-1 and σ-2) are non-opioid proteins implicated in the pathophysiology of various neurological disorders and cancer. The σ-1 subtype is a chaperon protein widely distributed in the CNS and peripheral tissues. These receptors are involved in the modulation of K(+)- and Ca(2+)-dependent signaling cascades at the endoplasmic reticulum and modulation of neurotransmitter release. σ-1 receptors are emerging targets for the treatment of neurophychiatric diseases (schizophrenia and depression) and cocaine addiction. σ-2 receptors are lipid raft proteins. They are highly expressed on many tumor cells and hence considered potential targets for anticancer drugs. σ receptors bind to a diverse class of pharmacological compounds like cocaine, methamphetamine, benzomorphans like (±)-pentazocine, (±)-SKF-10,047 and endogenous neurosteroids and sphingolipids. In this review we focus on the early development of σ receptor-specific ligands and radiolabeling agents.

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Regulating ankyrin dynamics: Roles of sigma-1 receptors

Cited by 256 publications

References 35 publications

Sigma-1 Receptor Expression in Sensory Neurons and the Effect of Painful Peripheral Nerve Injury

Sigma-1 Receptor Expression in Sensory Neurons and the Effect of Painful Peripheral Nerve Injury

Systems-level view of cocaine addiction: The interconnection of the immune and nervous systems

Early Development of Sigma-Receptor Ligands

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