Hemicholinium-3 (HC3) blocks the effects of ethylcholine mustard aziridinium (AF64A) in the developing rat. 1994

W G Brake, and B A Pappas
Life Science Research Centre, Carleton University, Ottawa, Canada.

Two- to 3-day-old rat pups received bilateral intracerebroventricular (i.c.v.) injections of 2.0 nmol/microliters AF64A or vehicle. Half of the pups had been preinjected i.c.v. with hemicholinium-3 (HC3) and the other half with saline. The administration of AF64A impaired spatial learning/memory and caused brain damage characterized by marked loss of forebrain cortical/subcortical tissue and ventricular hypertrophy when these were assessed in adulthood. Neither the behavioral nor the histopathological effects of AF64A were observed in rats that had been pretreated with HC3. Since HC3 is a potent and relatively selective inhibitor of high affinity choline uptake (HACU), the results indicate that the toxic effects of AF64A in the neonatal rat are dependent upon its uptake via the HACU site. If as other research suggests, this site is primarily on Ach neurons in the neonatal rat, then the consequences of neonatal damage to cholinergic neurons are severe for forebrain development.

UI MeSH Term Description Entries
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002794 Choline A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D002795 Choline O-Acetyltransferase An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 2.3.1.6. Choline Acetylase,Choline Acetyltransferase,Acetylase, Choline,Acetyltransferase, Choline,Choline O Acetyltransferase,O-Acetyltransferase, Choline
D006426 Hemicholinium 3 A potent inhibitor of the high affinity uptake system for CHOLINE. It has less effect on the low affinity uptake system. Since choline is one of the components of ACETYLCHOLINE, treatment with hemicholinium can deplete acetylcholine from cholinergic terminals. Hemicholinium 3 is commonly used as a research tool in animal and in vitro experiments. Hemicholinium
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D001388 Aziridines Saturated azacyclopropane compounds. They include compounds with substitutions on CARBON or NITROGEN atoms. Ethyleneimines,Azacyclopropanes, Saturated,Dimethyleneimines,Saturated Azacyclopropanes
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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