Kainic acid, or kainate, is an acid that naturally occurs in some

seaweed Seaweed, or macroalgae, refers to thousands of species of macroscopic, multicellular, marine algae. The term includes some types of '' Rhodophyta'' (red), ''Phaeophyta'' (brown) and ''Chlorophyta'' (green) macroalgae. Seaweed species such as ...

. Kainic acid is a potent neuroexcitatory amino acid

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

that acts by activating receptors for

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

, the principal excitatory

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

in the central nervous system. Glutamate is produced by the cell's metabolic processes and there are four major classifications of

glutamate receptors Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system an ...

NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

receptors,

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

receptors, kainate receptors, and the

metabotropic glutamate receptors The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate rece ...

. Kainic acid is an agonist for

kainate receptor Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug ...

s, a type of

ionotropic glutamate receptor Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in ...

. Kainate receptors likely control a

sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...

that produces

excitatory postsynaptic potential In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...

s (EPSPs) when glutamate binds. Kainic acid is commonly injected into laboratory animal models to study the effects of experimental ablation. Kainic acid is a direct agonist of the glutamic kainate receptors and large doses of concentrated solutions produce immediate neuronal death by overstimulating neurons to death. Such damage and death of neurons is referred to as an

excitotoxic In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate re ...

lesion. Thus, in large, concentrated doses kainic acid can be considered a neurotoxin, and in small doses of dilute solution kainic acid will chemically stimulate neurons. In fact, kainate seems to regulate serotonergic activity in the vertebrate retina. Electrical stimulation of designated areas of the brain are generally administered by passing an electric current through a wire that is inserted into the brain to lesion a particular area of the brain. Electrical stimulation indiscriminately destroys anything in the vicinity of the electrode tip, including neural bodies and axons of neurons passing through; therefore it is difficult to attribute the effects of the lesion to a single area. Chemical stimulation is typically administered through a cannula that is inserted into the brain via

stereotactic surgery Stereotactic surgery is a minimally invasive form of surgical intervention that makes use of a three-dimensional coordinate system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injec ...

. Chemical stimulation, while more complicated than electrical stimulation, has the distinct advantage of activating cell bodies, but not nearby axons, because only cell bodies and subsequent dendrites contain glutamate receptors. Therefore, chemical stimulation by kainic acid is more localized than electrical stimulation. Both chemical and electrical

lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

potentially cause additional damage to the brain due to the very nature of the inserted electrode or cannula. Therefore, the most effective ablation studies are performed in comparison to a sham lesion that duplicates all the steps of producing a brain lesion except the one that actually causes the brain damage, that is, injection of kainic acid or administration of an electrical shock.

Occurrence

Kainic acid was originally isolated from the

seaweeds Seaweed, or macroalgae, refers to thousands of species of macroscopic, multicellular, marine algae. The term includes some types of '' Rhodophyta'' (red), ''Phaeophyta'' (brown) and ''Chlorophyta'' (green) macroalgae. Seaweed species such as ...

Digenea simplex Digenea (Gr. ''Dis'' – double, ''Genos'' – race) is a class of trematodes in the Platyhelminthes phylum, consisting of parasitic flatworms (known as ''flukes'') with a syncytial tegument and, usually, two suckers, one ventral and one oral. ...

'' and '' Chondria armata'' in 1953. They are called "Kainin-sou" or "Makuri" in

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

, and are used as an

anthelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may a ...

Pharmacological activity

Kainic acid is utilised in primary neuronal cell cultures and in the acute brain slice preparation to study the physiological effect of excitotoxicity and assess the neuroprotective capabilities of potential therapeutics. Kainic acid is a potent

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

excitant that is used in epilepsy research to induce seizures in experimental animals, at a typical dose of 10–30 mg/kg in mice. In addition to inducing seizures, kainic acid is excitotoxic and epileptogenic. Kainic acid induces seizures via activation of

s containing the

GluK2 Glutamate ionotropic receptor kainate type subunit 2, also known as ionotropic glutamate receptor 6 or GluR6, is a protein that in humans is encoded by the ''GRIK2'' (or ''GLUR6'') gene. Function This gene encodes a subunit of a kainate glut ...

subunit and also through activation of AMPA receptors, for which it serves as a partial agonist. Also, infusion with kainic acid in the hippocampus of animals results in major damage of pyramidal neurons and subsequent seizure activity. Supply shortages beginning in 2000 have caused the cost of kainic acid to rise significantly.

Applications

* antiworming agent *

neuroscience Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...

research ** neurodegenerative agent ** modeling of

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

** modeling of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

References

External links

Kainate Receptors
{{Authority control Amino acids Pyrrolidines Convulsants Marine neurotoxins Kainate receptor agonists Chelating agents Toxic amino acids Dicarboxylic acids Excitotoxins Isopropenyl compounds

Occurrence

Pharmacological activity

Applications

See also

References

External links