An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the alpha 7 subtype.
The agonist properties of acetylcholine (ACh), tetramethylammonium, ethyl-trimethylammonium and choline were evaluated for muscle and neuronal nicotinic receptors in Xenopus oocytes. The only essential feature for a neuronal receptor agonist appears to be the charged nitrogen. For specific receptor subtypes, other structural elements appear permissive (neither increasing nor decreasing activity) or non-permissive (decreasing activity). Choline was a full agonist for alpha 7, but a hydroxyl group was strongly non-permissive for other receptor subtypes (alpha 1 beta 1 gamma delta, alpha 3 beta 4, alpha 3 beta 2, and alpha 4 beta 2). The binding of these ligands to brain membranes is consistent with the electrophysiological results. Physiological concentrations of choline desensitize alpha 7 receptors to ACh suggesting that, in vivo, choline may regulate both the activation and inactivation of this receptor.
Papke
R L
RL
Department of Pharmacology and Therapeutics, University of Florida, Gainesville 32610-0267, USA.
Bencherif
M
M
Lippiello
P
P
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002794:Choline / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D005260:Female; D008024:Ligands; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017672:Nitrogen Compounds / Q000494:pharmacology*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D012680:Sensitivity and Specificity; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014982:Xenopus laevis
D008024:Ligands; D018722:Nicotinic Agonists; D017672:Nitrogen Compounds; D000644:Quaternary Ammonium Compounds; D011978:Receptors, Nicotinic; D013757:Tetraethylammonium Compounds; C039795:trimethylethylammonium; D019789:Tetraethylammonium; D002794:Choline; D000109:Acetylcholine