RESUMO
In continuation of previous reports, it was found that the neurotrophic factor (NF) of the central nervous system of the cat for the maintenance of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7; AcChoEase) in the denervated cat superior cervical ganglion is a heat-stable compound of low molecular weight (less than 1,000) and that it is probably a peptide. Acetylcholine and nerve growth factor were eliminated as the NF; cyclic AMP produced an effect similar to that of the NF. The NF is probably not present in significant amounts in liver or skeletal muscle; it appears to be present in small intestine. It does not modify the AcChoEase content of the nondenervated cat superior cervical ganglion. Possible mechanisms of action of the NF are discussed.
Assuntos
Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Gânglios Simpáticos/enzimologia , Proteínas do Tecido Nervoso/isolamento & purificação , Animais , Gatos , Diferenciação Celular/efeitos dos fármacos , AMP Cíclico/farmacologia , Denervação , Fatores de Crescimento Neural/farmacologia , Teofilina/farmacologiaRESUMO
Experiments were designed to test the hypothesis that ganglionic butyrylcholinesterase (BuChE) is derived from acetylcholinesterase (AChE). At 5 to 8 days following preganglionic denervation of the right superior cervical ganglion (SCG), cats were given sarin, 2.0 mumol/kg, i.v. At intervals of 1 h and 1, 2, 3, 6, 11, and 22 days later, they were killed, and the AChE and BuChE contents of both SCG and both stellate ganglia (StG) were assayed. The regeneration of AChE in the normal ganglia occurred in two phases: an initial rapid phase, to 25-40% of control activity in 1 day, and a slow phase, to approximately 70% of control activity in 22 days. BuChE reached approximately 85% of control activity in normal SCG and StG at 22 days. In the denervated SCG, AChE activity reached a maximum of approximately 17% of normal at 1 day, the value prior to the administration of sarin, and did not increase appreciably above this subsequently. BuChE activity in the denervated SCG reached approximately 50% of normal ganglia at 22 days. At each interval, its activity approached 55% of that of the contralateral normal SCG, the value found in the denervated SCG prior to the administration of sarin. Hence, the regeneration of BuChE appears to be independent of the presence of AChE in the neuropil. The origin of ganglionic BuChE remains obscure.
Assuntos
Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Gânglios Simpáticos/enzimologia , Compostos Organofosforados/farmacologia , Sarina/farmacologia , Animais , Gatos , Denervação , Gânglios Simpáticos/efeitos dos fármacos , Cinética , Fatores de TempoRESUMO
The rates of regeneration of acetylcholinesterase (AChE) and propionylcholinesterase (PrChE) in the supernatants of aqueous homogenates of rat superior cervical ganglia, centrifuged at 100,000 g for 90 min, were determined at 1, 3, 6, and 16 h following their inactivation (greater than 90%) by administration of sarin, 2.0 mumol/kg i.v. Values were compared with those in animals in which the PrChE was continually suppressed by the repeated, fractional administration of iso-OMPA, in a total dose of 10 or 20 mumol/kg i.p. These doses of iso-OMPA alone produced 96-99% inactivation of PrChE with no detectable effect on AChE. Significant suppression of AChE regeneration by iso-OMPA administration was noted only at 6 h; in contrast with earlier findings in the cat, administration of iso-OMPA alone caused no significant increase in ganglionic AChE activity.
Assuntos
Acetilcolinesterase/metabolismo , Colinesterases/metabolismo , Gânglios Espinais/enzimologia , Compostos Organofosforados/farmacologia , Sarina/farmacologia , Animais , Feminino , Gânglios Espinais/efeitos dos fármacos , Cinética , Fosforilação , Ratos , Solubilidade , Frações Subcelulares/enzimologia , Tetraisopropilpirofosfamida/farmacologiaRESUMO
When homogenates of cat or rat superior cervical ganglia in Krebs-Ringer solution were incubated at 37 degrees C, the ensuing decrease in acetylcholinesterase (acetylcholine acylhydrolase, EC 3.1.1.7) activity was increased significantly by prior administration in vivo of tetramonoisopropylpyrophosphotetramide at doses that produced selective alkylphosphorylation of butyrylcholinesterase or propionylcholinesterase. These findings are consistent with the proposal that the latter enzymes are posttranscriptional precursors of acetylcholinesterase. Results of similar studies with homogenates of ganglia in water or in M NaCl/1% Triton X-100 were inconclusive, as were those of heat-inactivation studies and immunoprecipitation of the enzymes.