Alpha9 nicotinic acetylcholine receptors and the treatment of pain

• Autores: McIntosh, J. Michael; Absalom, Nathan; Chebib, Mary; Elgoyhen, Ana Belen; Vincler, Michelle
• Año de publicación: 2009
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: α-Conotoxin Vc1.1; α-Contoxin RgIA; Alpha9 nicotinic; GABA-B; Pain
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: McIntosh, J. Michael. University of Utah; Estados Unidos
Fil: Absalom, Nathan. The University of Sydney; Australia
Fil: Chebib, Mary. The University of Sydney; Australia
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: Vincler, Michelle. Wake Forest University Health Sciences; Estados Unidos