Artículo

McIntosh, J.M.; Absalom, N.; Chebib, M.; Elgoyhen, A.B.; Vincler, M. "Alpha9 nicotinic acetylcholine receptors and the treatment of pain" (2009) Biochemical Pharmacology. 78(7):693-702
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Abstract:

Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amounts of pain often remain. It is therefore highly desirable to develop treatments that work through distinct mechanisms of action. While agonists of nicotinic acetylcholine receptors (nAChRs) have been intensively studied, new data suggest a role for selective antagonists of nAChRs. α-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus. A subset of these peptides known as α-conotoxins RgIA and Vc1.1 produces both acute and long lasting analgesia. In addition, these peptides appear to accelerate the recovery of function after nerve injury, possibly through immune mediated mechanisms. Pharmacological analysis indicates that RgIA and Vc1.1 are selective antagonists of α9α10 nAChRs. A recent study also reported that these α9α10 antagonists are also potent GABA-B agonists. In the current study, we were unable to detect RgIA or Vc1.1 binding to or action on cloned GABA-B receptors expressed in HEK cells or Xenopus oocytes. We review the background, findings and implications of use of compounds that act on α9* nAChRs.11* indicates the possible presence of additional subunits. © 2009 Elsevier Inc. All rights reserved.

Registro:

Documento: Artículo
Título:Alpha9 nicotinic acetylcholine receptors and the treatment of pain
Autor:McIntosh, J.M.; Absalom, N.; Chebib, M.; Elgoyhen, A.B.; Vincler, M.
Filiación:Department of Psychiatry, University of Utah, Salt Lake City, UT 84132, United States
Department of Biology, University of Utah, Salt Lake City, UT 84112, United States
Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, 1428, Argentina
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, 1121, Argentina
Wake Forest University Health Sciences, Department of Anesthesiology, Winston-Salem, NC 27157, United States
Palabras clave:α-Conotoxin Vc1.1; α-Contoxin RgIA; Alpha9 nicotinic; GABA-B; Pain; 4 aminobutyric acid B receptor; 4 aminobutyric acid B receptor stimulating agent; alpha conotoxin; alpha conotoxin PeIA; alpha conotoxin rgia; alpha conotoxin Vc1.1; baclofen; calcium channel N type; nicotinic receptor; nicotinic receptor alpha10; nicotinic receptor alpha9; nicotinic receptor alpha9alpha10; nicotinic receptor alpha9alpha10 blocking agent; nicotinic receptor blocking agent; omega conotoxin MVIIA; unclassified drug; absence of side effects; allodynia; analgesic activity; antinociception; asthenia; central nervous system disease; chronic pain; clinical trial; confusion; diabetic neuropathy; dose response; drug efficacy; drug mechanism; drug potency; drug receptor binding; drug safety; drug selectivity; drug tolerance; human; hyperalgesia; immune response; multiple drug dose; nerve function; nerve injury; neuropathic pain; nonhuman; pain; priority journal; protein expression; receptor upregulation; repeated drug dose; review; sedation; side effect; single drug dose; Analgesics; Animals; Conotoxins; Humans; Nicotinic Agonists; Nicotinic Antagonists; Pain; Protein Multimerization; Protein Subunits; Receptors, GABA-B; Receptors, Nicotinic; Recombinant Proteins
Año:2009
Volumen:78
Número:7
Página de inicio:693
Página de fin:702
DOI: http://dx.doi.org/10.1016/j.bcp.2009.05.020
Título revista:Biochemical Pharmacology
Título revista abreviado:Biochem. Pharmacol.
ISSN:00062952
CODEN:BCPCA
CAS:baclofen, 1134-47-0; omega conotoxin MVIIA, 107452-89-1; Analgesics; CHRNA9 protein, human; Chrna9 protein, mouse; Chrna9 protein, rat; Conotoxins; Nicotinic Agonists; Nicotinic Antagonists; Protein Subunits; Receptors, GABA-B; Receptors, Nicotinic; Recombinant Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v78_n7_p693_McIntosh

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Citas:

---------- APA ----------
McIntosh, J.M., Absalom, N., Chebib, M., Elgoyhen, A.B. & Vincler, M. (2009) . Alpha9 nicotinic acetylcholine receptors and the treatment of pain. Biochemical Pharmacology, 78(7), 693-702.
http://dx.doi.org/10.1016/j.bcp.2009.05.020
---------- CHICAGO ----------
McIntosh, J.M., Absalom, N., Chebib, M., Elgoyhen, A.B., Vincler, M. "Alpha9 nicotinic acetylcholine receptors and the treatment of pain" . Biochemical Pharmacology 78, no. 7 (2009) : 693-702.
http://dx.doi.org/10.1016/j.bcp.2009.05.020
---------- MLA ----------
McIntosh, J.M., Absalom, N., Chebib, M., Elgoyhen, A.B., Vincler, M. "Alpha9 nicotinic acetylcholine receptors and the treatment of pain" . Biochemical Pharmacology, vol. 78, no. 7, 2009, pp. 693-702.
http://dx.doi.org/10.1016/j.bcp.2009.05.020
---------- VANCOUVER ----------
McIntosh, J.M., Absalom, N., Chebib, M., Elgoyhen, A.B., Vincler, M. Alpha9 nicotinic acetylcholine receptors and the treatment of pain. Biochem. Pharmacol. 2009;78(7):693-702.
http://dx.doi.org/10.1016/j.bcp.2009.05.020