Effects of Inactivation of Butyrylcholinesterase on Steady State and Regenerating Levels of Ganglionic Acetylcholinesterase

Abstract

Abstract— The effects of single and repeated injections of tetramonoisopropyl pyrophosphortetramide (iso‐OMPA), a selective inactivator of butyrylcholinesterase (BuChE), were studied on the ganglionic and muscular levels of BuChE and acetylcholinesterase (AChE) in cats during the steady state and following the irreversible inactivation of both enzymes by isopropylmethylphosphonofluoridate (sarin). Single intravenous injections of iso‐OMPA, 3.0 or 6.0 μmol/kg, produced nearly total inactivation of BuChE with no immediate effect on the AChE of the superior cervical (SCG), stellate (StG), and ciliary (CG) ganglia and inferior oblique (10) muscle; regeneration of BuChE occurred at approximately the same rate in the three ganglia, and at 4–6 days the AChE levels were significantly elevated. When single doses of iso‐OMPA were given 1 h following sarin, 2.0 μmol/kg, intravenously, there was a slight increase in the rate of AChE regeneration during the ensuing 2 days. With the repeated injection of iso‐OMPA, 3.0 μmol/kg every 48 h, there was a consistent but not statistically significant reduction in AChE regeneration at 4, 6, 12, and 18 days following sarin in all 3 ganglia. Similar treatment with iso‐OMPA alone produced significant increases in ganglionic AChE at all these periods excepting the longest. The daily injection of iso‐OMPA for 6 days, which maintained ganglionic BuChE at approx 2% of the control values, produced significant reductions in AChE regeneration, but again significant increases in ganglionic AChE levels in cats that did not receive sarin. The IO muscle did not exhibit these effects. A working hypothesis is proposed, that BuChE is a precursor of ganglionic AChE, and that the level of BuChE participates in the regulation of AChE synthesis by inhibition of a preceding rate‐limiting step.

Modulation of the Acetylcholine System in the Superior Cervical Ganglion of Rat: Effects of GABA and Hypoglossal Nerve Implantation After In Vivo GABA Treatment

“…Interestingly, no changes in the activity of the corresponding BuChE were observed (not shown). This observation supports the view (Klinar et al, 1983) that the two types of ChEs may be regulated by different mechanisms, although coregulation has been suggested by Silman et al (1979) and BuChE may be the precursor of AChE (Koelle et al, 1977). The behavior of the 16s AChE form in GABAtreated "hyperinnervated" ganglia resembles the regulation of this form by nerve growth factor (NGF) in neuronal tissue cultures (Rieger et al, 1980;Intestrosa et al, 1981;Verdikre and Rieger, 1982).…”

Cholinesterases modulate cell adhesion in human neuroblastoma cells in vitro

“…In the embryo, high levels of BChE are associated with proliferating, as opposed to aggregating and differentiating cells [1]. It has been proposed that BChE may reciprocally regulate AChE expression [48,49]. We were, however, unable to confirm this effect in neuroblastoma cells (data not shown).…”

Electron microscope localization of acetylcholinesterase and butyrylcholinesterase in the superior cervical ganglion of the cat. II. Preganglionically denervated ganglion.

“…This was originally suggested by the observation of the identical localization of the two enzymes on the ganglion cells of the cat SCG (1) . It is supported by the findings that the selective alkylphosphorylation of BuChE by iso-OMPA causes a decrease in the rate of regeneration of ganglionic ACNE in vivo after its inactivation by sarin (18), and an increase in the rate of disappearance of AChE in ganglionic homogenates in vitro (19).…”