Biomaterial Database

Cholinesterase inhibitors induce growth cone collapse and inhibit neurite extension in primary cultured chick neurons. 1998

S Saito

Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi, Japan.

Cholinesterase inhibitors are commonly prescribed medicines in neurological and anesthesiological clinical practices at relatively high doses. Recent studies report that cholinesterases, originally described as neurotransmitter degradation enzymes, are expressed in the developing central nervous systems. They are hypothesized to play an important role during the establishment of neuronal cytoarchitecture. In this study, the effects of several clinically utilized cholinesterase inhibitors on one potential aspect of neuronal development were examined using a primary culture system of chick central and peripheral neurons. Three cholinesterase inhibitors, physostigmine, neostigmine, and edrophonium, suppressed the activity of the leading edges of the extending axons (the nerve growth cones) dose dependently. Filopoda and lamellipodia of nerve growth cones were collapsed by the exposure to the cholinesterase inhibitors. This action was quick, mostly within 5 min, and partly irreversible. The lowest concentration that could induce statistically significant growth cone collapse was 10(-5) M for physostigmine, 10(-4) M for neostigmine, and 10(-2) for edrophonium, respectively. The ED50 values for the growth cone collapsing activity were approximately, 10(-3) M for physostigmine. 10(-2.5) M for neostigmine, and 10(-2) M for edrophonium both in dorsal root ganglion culture and in retinal culture. Even though the result of this in vitro study cannot be applied directly to the in vivo situation, physicians should consider the potential detrimental effects of cholinesterase inhibitors to growing and regenerating nervous tissues.

UI	MeSH Term	Description	Entries
D009388	Neostigmine	A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.	Synstigmin,Neostigmine Bromide,Neostigmine Methylsulfate,Polstigmine,Proserine,Prostigmin,Prostigmine,Prozerin,Syntostigmine,Bromide, Neostigmine,Methylsulfate, Neostigmine
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010830	Physostigmine	A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.	Eserine
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D002642	Chick Embryo	The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.	Embryo, Chick,Chick Embryos,Embryos, Chick
D002800	Cholinesterase Inhibitors	Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.	Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D004491	Edrophonium	A rapid-onset, short-acting cholinesterase inhibitor used in cardiac arrhythmias and in the diagnosis of myasthenia gravis. It has also been used as an antidote to curare principles.	Edrophonium Chloride,Edrophonium Bromide,Edroponium,Tensilon,Bromide, Edrophonium,Chloride, Edrophonium
D005727	Ganglia, Spinal	Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.	Dorsal Root Ganglia,Spinal Ganglia,Dorsal Root Ganglion,Ganglion, Spinal,Ganglia, Dorsal Root,Ganglion, Dorsal Root,Spinal Ganglion
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
D016501	Neurites	In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.	Neurite