A cyclic AMP analog and high potassium prevent the death of cultured septal cholinergic neurons after nerve growth factor withdrawal.
Survival, following the addition of a cAMP analog and high K+ to the medium, of cultured fetal septal cholinergic neurons was examined after nerve growth factor (NGF) deprivation. The number of acetylcholinesterase positive cells, which had progressively grown during 11-13 d of culture with NGF (50 ng/ml), was greatly reduced following 5 d of extended culture without NGF (55% of that with NGF). The degeneration of the cholinergic neurons was markedly reduced by addition of dibutyryl cAMP (dbcAMP, 1 mM), forskolin (10 microM) or KCl (15 mM) to the medium. K252b, which blocks the survival of NGF, had no effect on the action of dbcAMP. H-8 and nifedipine inhibited the survival of dbcAMP and high KCl, respectively. These results suggest that NGF, dbcAMP and high K+ promote the survival of septal cholinergic neurons acting via the receptor tyrosine kinase, protein kinase A and a Ca(2+)-dependent mechanism, respectively.
Takadera
T
T
Department of Biodynamics, Hokuriku University, Kanazawa, Japan.
Maki
T
T
Hibino
H
H
Mohri
T
T
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006651:Histocytochemistry; D026121:Indole Alkaloids; D009410:Nerve Degeneration / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000166:cytology* / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats
D002121:Calcium Channel Blockers; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D005576:Colforsin; D003994:Bucladesine; C049985:staurosporine aglycone; D011493:Protein Kinase C; D000110:Acetylcholinesterase; D009543:Nifedipine; D011188:Potassium