Interactions of anticholinesterases with Achatina fulica acetylcholine responses and electrogenic sodium pump.
The dose-dependent effects of the anticholinesterases, neostigmine and mycotoxin territrem-B, were determined on: (i) Cl(-)-responses of voltage clamped Achatina fulica neurons to microperfused acetylcholine; (ii) the 4 K(+)-induced outward currents evoked by an electrogenic sodium pump in the same neuron; and (iii) acetylcholinesterase activity of Achatina fulica ganglionic homogenates. Both compounds at low doses potentiated the peak acetylcholine responses. However, they had different effects at higher (> 1 microM) doses in that neostigmine now antagonized acetylcholine responses, while territrem-B still produced a maximal potentiation. At all doses neostigmine produced a dose-dependent inhibition of acetylcholinesterase activity. The cholinolytic effect of high doses of neostigmine was associated with the inhibition of 4 K(+)-induced current in the same neuron, while territrem-B neither altered the K(+)-induced current nor antagonized acetylcholine responses. The cholinolytic effect of neostigmine was completely antagonized by the inhibition of electrogenic sodium pump by ouabain or by perfusion with K(+)-free solution. These results suggest that neostigmine at high concentrations inhibits the electrogenic sodium pump and that the cholinolytic effect of high doses of neostigmine is secondary to this action. Territrem-B, on the other hand, had no effect on the electrogenic sodium pump and had no effect on the neuronal membrane properties other than to inhibit acetylcholinesterase. Thus, territrem-B may be a useful tool for studying the interaction between acetylcholinesterase and acetylcholine receptors.
Department of Pharmacology and Neurology, National Taiwan University, College of Medicine, Taipei, R.O.C.
V L
VL
Arvanov
H H
HH
Liou
Y C
YC
Chang
R C
RC
Chen
F C
FC
Peng
K H
KH
Ling
M C
MC
Tsai
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017952:Ganglia, Invertebrate / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009183:Mycotoxins / Q000494:pharmacology; D009388:Neostigmine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011714:Pyrans / Q000494:pharmacology*; D012908:Snails; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D009183:Mycotoxins; D011714:Pyrans; D009388:Neostigmine; D010042:Ouabain; C040405:territrem B; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine