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
Occurrenceedit
Kainic acid was originally isolated from the seaweedsDigenea simplex and Chondria armata in 1953.[5] They are called "Kainin-sou" or "Makuri" in Japan, and are used as an anthelmintic.
Pharmacological activityedit
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]
^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.
^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. PMC6574125. PMID 30995339.
^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. ISBN978-1-4939-0380-1.
^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.
^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.
^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. PMC3996208. PMID 24760837.
^Tremblay JF (2000). "Shortage of kainic acid hampers neuroscience research". Chemical & Engineering News Archive. Chemical and Engineering News. 78: 14–15. doi:10.1021/cen-v078n001.p014. Retrieved 22 February 2021.
^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 linksedit
December 13, 2023
kainic, acid, kainate, redirects, here, confused, with, kainite, kainate, acid, that, naturally, occurs, some, seaweed, potent, neuroexcitatory, amino, acid, agonist, that, acts, activating, receptors, glutamate, principal, excitatory, neurotransmitter, centra. Kainate redirects here Not to be confused with Kainite 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 NamesIUPAC name 3S 4S 3 Carboxymethyl 4 prop 1 en 2 yl L prolineSystematic IUPAC name 2S 3S 4S 3 Carboxymethyl 4 prop 1 en 2 yl pyrrolidine 2 carboxylic acidOther names 2 Carboxy 3 carboxymethyl 4 isopropenyl pyrrolidine citation needed IdentifiersCAS Number 487 79 6 Y3D model JSmol Interactive imageBeilstein Reference 86660ChEBI CHEBI 31746 YChEMBL ChEMBL27527 NChemSpider 9837 YKEGG C12819 NMeSH Kainic acidPubChem CID 10255UNII SIV03811UC YCompTox Dashboard EPA DTXSID7040526InChI 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 NKey VLSMHEGGTFMBBZ UHFFFAOYSA N NSMILES OC O C H 1NC C H C C C C H 1CC O OPropertiesChemical formula C 10H 15N O 4Molar mass 213 233 g mol 1Melting point 215 C 419 F 488 K decomposes log P 0 635Acidity pKa 2 031Basicity pKb 11 966StructureCrystal structure MonoclinicExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references 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 Contents 1 Biosynthesis 2 Occurrence 3 Pharmacological activity 4 Applications 5 See also 6 References 7 External linksBiosynthesis editIn 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 a ketoglutarate aKG 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 nbsp Biosynthesis of kainic acid and kainic acid lactoneOccurrence editKainic 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 editKainic 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 Applications editneuroscience research neurodegenerative agent modeling of epilepsy 12 modeling of Alzheimer s diseaseSee also editDihydrokainic acid Domoic acid Kainate receptorReferences edit Carlson NR 2013 Physiology of Behavior Pearson pp 121 ISBN 978 0 205 23939 9 Carlson NR 2013 Physiology of Behavior Pearson pp 152 ISBN 978 0 205 23939 9 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 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 Moloney MG April 1998 Excitatory amino acids Natural Product Reports 15 2 205 219 doi 10 1039 a815205y PMID 9586226 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 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 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 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 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 Tremblay JF 2000 Shortage of kainic acid hampers neuroscience research Chemical amp Engineering News Archive Chemical and Engineering News 78 14 15 doi 10 1021 cen v078n001 p014 Retrieved 22 February 2021 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 editKainate Receptors Retrieved from https en wikipedia org w index php title Kainic acid amp oldid 1180716114, wikipedia, wiki, book, books, library,
