Publication: Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue
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Identifiers
Date
2020-12-28
Authors
Cortés-Montero, Elsa
Rodríguez-Muñoz, María
Ruiz-Cantero, María Del Carmen
Cobos, Enrique José
Sánchez-Blázquez, Pilar
Garzón-Niño, Javier
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Transient receptor potential ankyrin member 1 (TRPA1) belongs to the family of thermo TRP cation channels that detect harmful temperatures, acids and numerous chemical pollutants. TRPA1 is expressed in nervous tissue, where it participates in the genesis of nociceptive signals in response to noxious stimuli and mediates mechanical hyperalgesia and allodynia associated with different neuropathies. The glutamate N-methyl-d-aspartate receptor (NMDAR), which plays a relevant role in allodynia to mechanical stimuli, is connected via histidine triad nucleotide-binding protein 1 (HINT1) and type 1 sigma receptor (σ1R) to mu-opioid receptors (MORs), which mediate the most potent pain relief. Notably, neuropathic pain causes a reduction in MOR antinociceptive efficacy, which can be reversed by blocking spinal NMDARs and TRPA1 channels. Thus, we studied whether TRPA1 channels form complexes with MORs and NMDARs that may be implicated in the aforementioned nociceptive signals. Our data suggest that TRPA1 channels functionally associate with MORs, delta opioid receptors and NMDARs in the dorsal root ganglia, the spinal cord and brain areas. These associations were altered in response to pharmacological interventions and the induction of inflammatory and also neuropathic pain. The MOR-TRPA1 and NMDAR-TRPA1 associations do not require HINT1 or σ1R but appear to be mediated by calcium-activated calmodulin. Thus, TRPA1 channels may associate with NMDARs to promote ascending acute and chronic pain signals and to control MOR antinociception.
Description
MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Calcium-Binding Proteins::Intracellular Calcium-Sensing Proteins::Calmodulin
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathological Conditions, Anatomical::Constriction, Pathologic
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Aldehydes::Formaldehyde
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidic::Glutamates::Glutamic Acid
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Anatomy::Nervous System::Nerve Tissue
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Pain::Neuralgia
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Organ Specificity
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein Binding
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein Subunits
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion Channels::Ligand-Gated Ion Channels::Receptors, Ionotropic Glutamate::Receptors, N-Methyl-D-Aspartate
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Opioid
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Transport Proteins::Ion Channels::Calcium Channels::TRPP Cation Channels
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Sensation Disorders::Somatosensory Disorders::Hyperalgesia
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Opioid::Receptors, sigma
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Perception::Pain Perception::Nociception
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Perception::Pain Perception::Nociception
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Ankyrins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Histidine
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Opioid::Receptors, Opioid, delta
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Pain::Chronic Pain
Medical Subject Headings::Anatomy::Nervous System::Ganglia::Ganglia, Sensory::Ganglia, Spinal
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Spinal Cord
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Analgesics
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleotides
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidic::Glutamates
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Calcium-Binding Proteins::Intracellular Calcium-Sensing Proteins::Calmodulin
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathological Conditions, Anatomical::Constriction, Pathologic
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Aldehydes::Formaldehyde
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidic::Glutamates::Glutamic Acid
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Anatomy::Nervous System::Nerve Tissue
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Pain::Neuralgia
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Organ Specificity
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein Binding
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein Subunits
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion Channels::Ligand-Gated Ion Channels::Receptors, Ionotropic Glutamate::Receptors, N-Methyl-D-Aspartate
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Opioid
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Transport Proteins::Ion Channels::Calcium Channels::TRPP Cation Channels
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Sensation Disorders::Somatosensory Disorders::Hyperalgesia
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Opioid::Receptors, sigma
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Perception::Pain Perception::Nociception
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Perception::Pain Perception::Nociception
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Ankyrins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Histidine
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Opioid::Receptors, Opioid, delta
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Pain::Chronic Pain
Medical Subject Headings::Anatomy::Nervous System::Ganglia::Ganglia, Sensory::Ganglia, Spinal
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Spinal Cord
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Analgesics
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleotides
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidic::Glutamates
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
DeCS Terms
CIE Terms
Keywords
Transient receptor potential A1, Mu opioid receptor, Calmodulin, Glutamate NMDA receptor, Neuropathic pain, Inflammatory pain, Hyperalgesia, Antinociception, Dorsal root ganglia, Spinal cord, Canal catiónico TRPA1, Receptores opioides mu, Calmodulina, Receptores de glutamato, Neuralgia, Hiperalgesia, Ganglios espinales, Médula espinal
Citation
Cortés-Montero E, Rodríguez-Muñoz M, Ruiz-Cantero MDC, Cobos EJ, Sánchez-Blázquez P, Garzón-Niño J. Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue. Int J Mol Sci. 2020 Dec 28;22(1):229