INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
artículos
Título:
Alpha9 nicotinic acetylcholine receptors and the treatment of pain
Autor/es:
MCINTOSH JM; ABSALOM M; CHEBIB N; ELGOYHEN AB; VINCLER M
Revista:
BIOCHEMICAL PHARMACOLOGY
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2009 vol. 78 p. 693 - 702
ISSN:
0006-2952
Resumen:
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.  a-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus.  A subset of these peptides known as a-conotoxins RgIA and Vc1.1 produce 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 a9a10 nAChRs.  A recent study also reported that these a9a10 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 a9* nAChRs.