Effects of acetylcholinesterase and butyrylcholinesterase on cell survival, neurite outgrowth, and voltage-dependent calcium currents of embryonic ventral mesencephalic neurons.
The aim of this study was to investigate the effect of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) on cell survival, neurite outgrowth and voltage-dependent calcium currents in developing rat ventral mesencephalic (VM) neurons. Both BuChE and AChE have been shown to promote neurite outgrowth in postnatnal preparations. However, the effect of these substances has never been investigated on rat embryonic VM cells, which are used in animal models of foetal transplantation as a treatment for Parkinson's disease. The effects of incubation with BuChE and tetrameric (G(4))- or monomeric (G(1))-AChE on cell survival and neurite outgrowth were characterised over a 7-day period on dopaminergic cells within embryonic VM cultures. The acute effects of these treatments on voltage-dependent calcium currents from embryonic VM cells were then investigated using whole-cell voltage-clamp recordings. The chronic effect of modulating voltage-dependent calcium channels was subsequently explored using the selective calcium channel antagonists omega-agatoxin IVA, omega-conotoxin GVIA, and nifedipine. The results presented here demonstrate firstly trophic effects of BuChE and G(4)- and G(1)-AChE upon dopaminergic neurite outgrowth, secondly that BuChE and G(4)- and G(1)-AChE have an inhibitory effect on voltage-dependent calcium currents, and finally that selective voltage-dependent calcium channel inhibitors also have trophic effects upon dopaminergic neurite outgrowth.
Whyte
Kathryn A
KA
Department of Pharmacology, University of Oxford, Mansfield Road, OX1 3QT, Oxford, UK.
Greenfield
Susan A
SA
D000110:Acetylcholinesterase / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003470:Culture Media; D020866:omega-Conotoxin GVIA; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D009543:Nifedipine