Nicotinic acetylcholine receptor agonists promote survival and reduce apoptosis of chick ciliary ganglion neurons.
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.
Pugh
P C
PC
Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo, Ohio 43614, USA.
Margiotta
J F
JF
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*
D009479:Neuropeptides; D018722:Nicotinic Agonists; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011978:Receptors, Nicotinic; D011189:Potassium Chloride; D009538:Nicotine; D002217:Carbachol; D002714:Chlorisondamine