title: Nicotinic acetylcholine receptor agonists promote survival and reduce apoptosis of chick ciliary ganglion neurons.
abstract: The abundance, diversity, and ubiquitous expression of neuronal nicotinic acetylcholine receptors (AChRs) suggest that many are involved in functions other than synaptic transmission. We now report that a major AChR class promotes neuronal survival. The 10-day survival of ciliary ganglion neurons in basal culture medium (MEM) was approximately 35%, but increased to approximately 75% in MEM containing nicotine (MEM/Nic) or carbachol, an effect similar to that achieved by chronic depolarization with KCl. Pharmacological experiments revealed that agonist-enhanced survival requires activation of AChRs sensitive to alpha-bungarotoxin (alphaBgt). alphaBgt-AChRs partly support neuronal survival by limiting apoptosis since fewer apoptotic neurons were observed in MEM/Nic compared to MEM. Moreover, nicotinic survival support was not further enhanced by fibroblast growth factor, as seen for KCl, but increased to 100% by adding PACAP, a trophic neuropeptide present in the ganglion. These results indicate that alphaBgt-AChR activation regulates neuronal survival and suggest a mechanism involving reduced apoptosis and interaction with an endogenous neuropeptide growth factor.
authors.affiliation: Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo, Ohio 43614, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Pugh
authors.forename: J F
authors.initials: JF
authors.lastname: Margiotta
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002714:Chlorisondamine / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011189:Potassium Chloride / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D009479:Neuropeptides; D018722:Nicotinic Agonists; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011978:Receptors, Nicotinic; D011189:Potassium Chloride; D009538:Nicotine; D002217:Carbachol; D002714:Chlorisondamine