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Effects of neostigmine and physostigmine on the acetylcholine receptor‐ionophore complex in frog isolated sympathetic neurones
Author(s) -
JunIchi Sadoshima,
Tokutomi Naofumi,
Akaike Norio
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11568.x
Subject(s) - physostigmine , neostigmine , chemistry , acetylcholine , cholinesterase , atropine , acetylcholinesterase , acetylcholinesterase inhibitor , acetylcholine receptor , pharmacology , biophysics , endocrinology , receptor , biochemistry , medicine , biology , enzyme
1 The effects of neostigmine and physostigmine, reversible carbamate acetylcholinesterase (AChE)‐inhibitors, on nicotinic acetylcholine‐induced inward currents (IACH) were investigated in enzymatically isolated single sympathetic ganglion cells from the bullfrog. The ‘concentration clamp’ technique which combines intracellular perfusion with a rapid external solution change under single electrode voltage‐clamp conditions was used. 2 Pretreatment with neostigmine and physostigmine did not enhance I Ach at any concentrations, suggesting that AChE activity had already disappeared during the enzymatic treatment of the preparation. 3 Both neostigmine and physostigmine inhibited I Ach in a dose‐dependent manner with IC 50 values of 7.0 × 10 −4 m and 1.1 × 10 −4 m , respectively. The blockade by neostigmine was competitive, while that by physostigmine was non‐competitive. 4 The inhibition of I Ach by neostigmine and physostigmine showed no apparent voltage dependency. 5 Neostigmine did not cause obvious changes of the kinetics of I Ach . However, physostigmine reduced both the fast and slow time constants of inactivation of I Ach , thus facilitating the rate of inactivation without affecting the activation kinetics of I Ach.6 These results suggest that neostigmine and physostigmine have different direct actions on the ACh receptor‐ionophore complex. Neostigmine may act on the ACh‐receptor (the binding site of ACh) while physostigmine may interact with the ACh‐gated cation channels.