Jump to content

Kainic acid

From Wikipedia, the free encyclopedia
Kainic acid
Stereo, skeletal formula of kainic acid
IUPAC name
Systematic IUPAC name
(2S,3S,4S)-3-(Carboxymethyl)-4-(prop-1-en-2-yl)pyrrolidine-2-carboxylic acid
Other names
2-Carboxy-3-carboxymethyl-4-isopropenyl-pyrrolidine[citation needed]
3D model (JSmol)
MeSH Kainic+acid
  • InChI=1S/C10H15NO4/c1-5(2)7-4-11-9(10(14)15)6(7)3-8(12)13/h6-7,9,11H,1,3-4H2,2H3,(H,12,13)(H,14,15) ☒N
  • OC(=O)[C@H]1NC[C@H](C(C)=C)[C@@H]1CC(=O)O
Molar mass 213.233 g·mol−1
Melting point 215 °C (419 °F; 488 K) (decomposes)
log P 0.635
Acidity (pKa) 2.031
Basicity (pKb) 11.966
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervous system. Glutamate is produced by the cell's metabolic processes and there are four major classifications of glutamate receptors: NMDA receptors, AMPA receptors, kainate receptors, and the metabotropic glutamate receptors. Kainic acid is an agonist for kainate receptors, a type of ionotropic glutamate receptor. Kainate receptors likely control a sodium channel that produces excitatory postsynaptic potentials (EPSPs) when glutamate binds.[1]

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 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.[2] In fact, kainate seems to regulate serotonergic activity in the vertebrate retina.[3]

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. 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 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.


In 2019, Chekan et al. were able to use bioinformatic tools to look for domoic acid gene homologs in the seaweed Digenea simplex.[4] Researchers identified a cluster containing genes identified as the kainic acid biosynthesis (kab) genes. This cluster contains an annotated N-prenyltransferase, α-ketoglutarate (αKG)-dependent dioxygenase, and several retrotransposable elements. To confirm production of kainic acid through the identified cluster, Chekan et al. expressed the genes in Escherichia coli and validated the enzymatic functions of each proposed gene.

The first step of the pathway involves the N-prenyltransferase, KabA, which allows for the prenylation of L-glutamic acid with dimethylallyl pyrophosphate (DMAPP) to form the intermediate N-dimethylallyl-l-glutamic acid (prekainic acid). KabC then catalyzes the stereocontrolled formation of the trisubstituted pyrrolidine ring, taking prekainic acid to the final kainic acid. KabC was also able to produce another kainic acid isomer, kainic acid lactone.

Biosynthesis of kainic acid and kainic acid lactone


Kainic acid was originally isolated from the seaweeds Digenea simplex and Chondria armata in 1953.[5] They are called "Kainin-sou" or "Makuri" in Japan, and are used as an anthelmintic.

Pharmacological activity[edit]

Kainic acid is utilised in primary neuronal cell cultures[6] and in the acute brain slice preparation[7] to study the physiological effect of excitotoxicity and assess the neuroprotective capabilities of potential therapeutics.

Kainic acid is a potent central nervous system excitant that is used in epilepsy research to induce seizures in experimental animals,[8] at a typical dose of 10–30 mg/kg in mice. In addition to inducing seizures, kainic acid is excitotoxic and epileptogenic.[9] Kainic acid induces seizures via activation of kainate receptors containing the GluK2 subunit and also through activation of AMPA receptors, for which it serves as a partial agonist.[10] 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.[11]


See also[edit]


  1. ^ Carlson NR (2013). Physiology of Behavior. Pearson. pp. 121. ISBN 978-0-205-23939-9.
  2. ^ Carlson NR (2013). Physiology of Behavior. Pearson. pp. 152. ISBN 978-0-205-23939-9.
  3. ^ Passos AD, Herculano AM, Oliveira KR, de Lima SM, Rocha FA, Freitas HR, et al. (October 2019). "Regulation of the Serotonergic System by Kainate in the Avian Retina". Cellular and Molecular Neurobiology. 39 (7): 1039–1049. doi:10.1007/s10571-019-00701-8. PMID 31197744. S2CID 254384979.
  4. ^ Chekan JR, McKinnie SM, Moore ML, Poplawski SG, Michael TP, Moore BS (June 2019). "Scalable Biosynthesis of the Seaweed Neurochemical, Kainic Acid". Angewandte Chemie. 58 (25): 8454–8457. doi:10.1002/anie.201902910. PMC 6574125. PMID 30995339.
  5. ^ Moloney MG (April 1998). "Excitatory amino acids". Natural Product Reports. 15 (2): 205–219. doi:10.1039/a815205y. PMID 9586226.
  6. ^ Meade AJ, Meloni BP, Mastaglia FL, Watt PM, Knuckey NW (November 2010). "AP-1 inhibitory peptides attenuate in vitro cortical neuronal cell death induced by kainic acid". Brain Research. 1360: 8–16. doi:10.1016/j.brainres.2010.09.007. PMID 20833150. S2CID 42116946.
  7. ^ Craig AJ, Housley GD, Fath T (2014). "Modeling excitotoxic ischemic brain injury of cerebellar Purkinje neurons by intravital and in vitro multi-photon laser scanning microscopy.". In Bakota L, Brandt R (eds.). Laser scanning microscopy and quantitative image analysis of neuronal tissue. Springer. pp. 105–128. ISBN 978-1-4939-0380-1.
  8. ^ Barrow PA. A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy. OCLC 53634796.
  9. ^ Ben-Ari Y (2012). "Kainate and Temporal Lobe Epilepsies: 3 decades of progress". In Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds.). Jasper's Basic Mechanisms of the Epilepsies [Internet] (4th ed.). Bethesda (MD): National Center for Biotechnology Information (US). PMID 22787646.
  10. ^ Fritsch B, Reis J, Gasior M, Kaminski RM, Rogawski MA (April 2014). "Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis". The Journal of Neuroscience. 34 (17): 5765–5775. doi:10.1523/JNEUROSCI.5307-13.2014. PMC 3996208. PMID 24760837.
  11. ^ Tremblay JF (2000). "Shortage of kainic acid hampers neuroscience research". Chemical & Engineering News Archive. 78. Chemical and Engineering News: 14–15. doi:10.1021/cen-v078n001.p014. Retrieved 22 February 2021.
  12. ^ Barrow PA. A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy. OCLC 53634796.

External links[edit]