Hemicholinium-3
Encyclopedia
Hemicholinium-3 also known as hemicholine, is a drug
which blocks the reuptake
of choline
by the high affinity transporter ChT (encoded in humans by the gene SLC5A7) at the presynapse
. The reuptake of choline is the rate limiting step in the synthesis of acetylcholine
; hence, hemicholinium-3 decreases the synthesis of acetylcholine. It is therefore classified as an indirect
acetylcholine antagonist.
Acetylcholine is synthesized from choline and a donated acetyl
group from acetyl-CoA
, by the action of choline acetyltransferase
(ChAT). Thus, decreasing the amount of choline available to a neuron will decrease the amount of acetylcholine produced. Neurons affected by hemicholinium-3 must rely on the transport of choline from the soma
(cell body), rather than relying on reuptake of choline from the synaptic cleft.
experiments.
Hemoicholinium-3 produces a decrease in acetylcholine content in the nerve terminal and as a consequence results in a decrease in acetylcholine transmission. Since acetylcholine normally binds to nicotinic and muscarinic receptors in synapses, a decrease in acetylcholine would cause a decrease in nicotinic and muscarinic pharmacology.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
which blocks the reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
of choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
by the high affinity transporter ChT (encoded in humans by the gene SLC5A7) at the presynapse
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...
. The reuptake of choline is the rate limiting step in the synthesis of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
; hence, hemicholinium-3 decreases the synthesis of acetylcholine. It is therefore classified as an indirect
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
acetylcholine antagonist.
Acetylcholine is synthesized from choline and a donated acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
group from acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
, by the action of choline acetyltransferase
Choline acetyltransferase
Choline acetyltransferase is an enzyme that is synthesized within the body of a neuron. It is then transferred to the nerve terminal via axoplasmic flow. The role of choline acetyltransferase is to join Acetyl-CoA to choline, resulting in the formation of the neurotransmitter acetylcholine...
(ChAT). Thus, decreasing the amount of choline available to a neuron will decrease the amount of acetylcholine produced. Neurons affected by hemicholinium-3 must rely on the transport of choline from the soma
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...
(cell body), rather than relying on reuptake of choline from the synaptic cleft.
Effects
Hemicholinium-3 has no clinical use, but is frequently used as a research tool in animal and in vitroIn vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
experiments.
Hemoicholinium-3 produces a decrease in acetylcholine content in the nerve terminal and as a consequence results in a decrease in acetylcholine transmission. Since acetylcholine normally binds to nicotinic and muscarinic receptors in synapses, a decrease in acetylcholine would cause a decrease in nicotinic and muscarinic pharmacology.