Brief exposure to neurotrophins produces a calcium-dependent increase in choline acetyltransferase activity in cultured rat septal neurons.
We demonstrate that brief (30-min) exposure of cultured embryonic rat septal neurons to neurotrophins (NTs) increases choline acetyltransferase (ChAT) activity by 20-50% for all tested NTs (nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4, each at 100 ng/ml). The increase in ChAT activity was first detected 12 h after NT exposure, persisted at least 48 h, and was not mediated by increased neuronal survival or action-potential activity. Under some conditions, the response to brief NT exposure was as great as that produced by continuous exposure. NT stimulation of ChAT activity was inhibited by inhibitors of p75- and Trk kinase-mediated signaling, by removal of extracellular Ca2+ during the period of NT exposure, and by buffering intracellular Ca2+ with BAPTA. Application of nerve growth factor and brain-derived neurotrophic factor transiently increased [Ca2+] within a subpopulation of neurons. NT stimulation of ChAT activity was not affected significantly by cyclic AMP agonists or antagonists. These findings suggest that brief exposure to NTs can have a long-lasting effect on cholinergic transmission, and that this effect requires Ca2+, but not cyclic AMP.
Nonner
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Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33101, USA.
Barrett
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EF
Barrett
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JN
D000818:Animals; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000502:physiology; D020917:Receptor, trkA / Q000502:physiology; D012688:Septum Pellucidum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium