Abstract—
The regeneration of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was followed in the superior cervical (SCG), stellate (StG), and ciliary (CG) ganglia and inferior oblique (IO) muscle of cats for the 3‐day period following their inactivation by isopropylmethylphosphonofluoridate (sarin; 2.0 μmol/kg intravenously), with and without preservation of over half the butyrylcholinesterase activity by the prior intravenous infusion of 10‐(α‐diethylaminopropionyl) phenothiazine HCl (Astra 1397; 100 or 200 μmol/kg). Rates of regeneration of AChE in the three ganglia exhibited the same sequence as their relative proportions of AChE‐containing cholinergic ganglion cells (SCG < StG < CG); no such difference was found in the rates of butyrylcholinesterase regeneration. The mean AChE levels in all three ganglia were higher at 48 h in the cats that had received Astra 1397 (100 μmol/kg) prior to sarin. This finding is interpreted as evidence that BuChE may function as a precursor in the synthesis of AChE.
Fixation of cat stellate ganglia by perfusion in situ with cold 4% formaldehyde in Krebs-Ringer solution, followed by immersion in the same solution for 3 or 6 hr, produced inactivation of approximately one-half the acetylcholinesterase (AChE) and butyrocholinesterase (BuChE); after 21 hr, further inactivation occurred. Similar fixation with glutaraldehyde (1, 2 and 4%) inactivated over three-quarters of the AChE and BuChE at 3 hr. but there was little further loss after 21 hr. Following sectioning of the preganglionic trunk, the AChE activity of the cat superior cervical ganglion fell to approximately 20%, and BuChE fell to approximately 50%; this confirms an early report by Sawyer and Hollinshead, which has been questioned in part because of subsequent histochemical findings. The basis for the discrepancy is discussed, along with its bearing on the interpretation of histochemical observations in general.
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.
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