9/25/2016 Neurotransmitters

Neurotransmitters
Dr.C.GeorgeBoeree

Neurotransmittersarethechemicalswhichallowthetransmissionofsignalsfromoneneurontothenext
acrosssynapses.Theyarealsofoundattheaxonendingsofmotorneurons,wheretheystimulatethemuscle
fibers.Andtheyandtheircloserelativesareproducedbysomeglandssuchasthepituitaryandtheadrenal
glands.Inthischapter,wewillreviewsomeofthemostsignificantneurotransmitters.

Acetylcholine

Acetylcholinewasthefirstneurotransmittertobediscovered.Itwasisolatedin1921byaGermanbiologist
namedOttoLoewi,whowouldlaterwintheNobelPrizeforhiswork.Acetylcholinehasmanyfunctions:It
isresponsibleformuchofthestimulationofmuscles,includingthemusclesofthegastrointestinalsystem.
Itisalsofoundinsensoryneuronsandintheautonomicnervoussystem,andhasapartinschedulingREM
(dream)sleep.

Theplantpoisonscurareandhemlockcauseparalysisbyblockingtheacetylcholinereceptorsitesofmuscle
cells.Thewellknownpoisonbotulinworksbypreventingthevesiclesintheaxonendingfromreleasing
acetylcholine,causingparalysis.Thebotulinderivativebotoxisusedbymanypeopletotemporarily
eliminatewrinklesasadcommentaryonourtimes,Iwouldsay.Onamoreseriousnote,thereisalink
betweenacetylcholineandAlzheimer'sdisease:Thereissomethingontheorderofa90%lossof
acetylcholineinthebrainsofpeoplesufferingfromAlzheimer's,whichisamajorcauseofsenility.

Norepinephrine

In1946,aSwedishbiologistbythenameofUlfvonEulerdiscoverednorepinephrine(formerlycalled
noradrenalin).HealsowonaNobelPrize.Norepinephrineisstronglyassociatedwithbringingournervous
systemsinto"highalert."Itisprevalentinthesympatheticnervoussystem,anditincreasesourheartrate
andourbloodpressure.Ouradrenalglandsreleaseitintothebloodstream,alongwithitscloserelative
epinephrine(akaadrenalin).Itisalsoimportantforformingmemories.

Stresstendstodepleteourstoreofadrenalin,whileexercisetendstoincreaseit.Amphetamines("speed")
workbycausingthereleaseofnorepinephrine,aswellasotherneurotransmitterscalleddopamineand
seratonin..

Dopamine

Anotherrelativeofnorepinephrineandepinephrineisdopamine,discoveredtobeaneurotransmitterinthe
1950sbyanotherSwede,ArvidCarlsson.Itisaninhibitoryneurotransmitter,meaningthatwhenitfindsits
waytoitsreceptorsites,itblocksthetendencyofthatneurontofire.Dopamineisstronglyassociatedwith
rewardmechanismsinthebrain.Drugslikecocaine,opium,heroin,andalcoholincreasethelevelsof
dopamine,asdoesnicotine.Ifitfeelsgood,dopamineneuronsareprobablyinvolved!

Theseverementalillnessschizophreniahasbeenshowntoinvolveexcessiveamountsofdopamineinthe
frontallobes,anddrugsthatblockdopamineareusedtohelpschizophrenics.Ontheotherhand,toolittle
dopamineinthemotorareasofthebrainareresponsibleforParkinson'sdisease,whichinvolves
uncontrollablemuscletremors.ItwasthesameArvidCarlssonmentionedabovewhofiguredoutthatthe
precursortodopamine(calledLdopa)couldeleviatesomeofthesymptomsofParkinson's.Hewasawarded
theNobelPrizein2000.

Recently,ithasbeennotedthatlowdopaminemayrelatednotonlytotheunsociabilityofschizophrenics,
butalsotosocialanxiety.Ontheotherhand,dopaminehasbeenfoundtohaverelativelylittletodowiththe
pleasuresofeating.Thatseemstoinvolvechemicalssuchasendorphin(seebelow).
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GABA

In1950,EugeneRobertsandJ.AwaparadiscoveredGABA(gammaaminobutyricacid),whichisalso
usuallyaninhibitoryneurotransmitter.GABAactslikeabraketotheexcitatoryneurotransmittersthatlead
toanxiety.PeoplewithtoolittleGABAtendtosufferfromanxietydisorders,anddrugslikeValiumworkby
enhancingtheeffectsofGABA.LotsofotherdrugsinfluenceGABAreceptors,includingalcoholand
barbituates.IfGABAislackingincertainpartsofthebrain,epilepsyresults.

Glutamate

GlutamateisanexcitatoryrelativeofGABA.Itisthemostcommonneurotransmitterinthecentralnervous
systemasmuchashalfofallneuronsinthebrainandisespeciallyimportantinregardstomemory.
Curiously,glutamateisactuallytoxictoneurons,andanexcesswillkillthem.Sometimesbraindamageora
strokewillleadtoanexcessandendwithmanymorebraincellsdyingthanfromtheoriginaltrauma.ALS,
morecommonlyknownasLouGehrig'sdisease,resultsfromexcessiveglutamateproduction.Manybelieve
itmayalsoberesponsibleforquiteavarietyofdiseasesofthenervoussystem,andarelookingforwaysto
minimizeitseffects

GlutamatewasdiscoveredbyKikunaeIkedaofTokayImperialUniv.in1907,whilelookingfortheflavor
commontothingslikecheese,meat,andmushrooms.Hewasabletoextractanacidfromseaweed
glutamate.HewentontoinventthewellknownseasoningMSGmonosodiumglutamate.Ittookdecades
forPeterUsherwoodtoidentifyglutamateasaneurotransmitter(inlocusts)in1994.

Serotonin

Serotoninisaninhibitoryneurotransmitterthathasbeenfoundtobeintimatelyinvolvedinemotionand
mood.Toolittleserotoninhasbeenshowntoleadtodepression,problemswithangercontrol,obsessive
compulsivedisorder,andsuicide.Toolittlealsoleadstoanincreasedappetiteforcarbohydrates(starchy
foods)andtroublesleeping,whicharealsoassociatedwithdepressionandotheremotionaldisorders.Ithas
alsobeentiedtomigraines,irritablebowelsyndrome,andfibromyalgia.

VittorioErspamerfirstdiscoveredwhatwenowcallseratonininthe1930s.Itwasfoundinbloodserumin
1948byIrvinePage,whonameditserotonin(fromserumtonic).AnotherresearcherinPageslab
MauriceRapportprovedthatitwasanamine(agroupofchemicalsthatincludetheneurotransmitters).
JohnWelshfoundthatitwasaneurotransmitterinmolluscsin1954,andBettyTwarog(alsoatPage'slab)
founditinvertebratesin1952.Allthisgivesyouasenseofthecooperativenatureofmostofscientific
discovery!

Prozacandotherrecentdrugshelppeoplewithdepressionbypreventingtheneuronsfrom"vacuuming"up
excessseratonin,sothatthereismoreleftfloatingaroundinthesynapses.Itisinterestingthatalittlewarm
milkbeforebedtimealsoincreasesthelevelsofseratonin.Asmommayhavetoldyou,ithelpsyoutosleep.
Serotoninisaderivativeoftryptophan,whichisfoundinmilk.The"warm"partisjustforcomfort!

Ontheotherhand,serotoninalsoplaysaroleinperception.HallucinogenssuchasLSD,mescaline,
psilocybin,andecstasyworkbyattachingtoseratoninreceptorsitesandtherebyblockingtransmissionsin
perceptualpathways.

Endorphin

In1973,SolomonSnyderandCandacePertofJohnsHopkinsdiscoveredendorphin.Endorphinisshortfor
"endogenousmorphine."Itisstructurallyverysimilartotheopioids(opium,morphine,heroin,etc.)andhas
similarfunctions:Inhibitory,itisinvolvedinpainreductionandpleasure,andtheopioiddrugsworkby
attachingtoendorphin'sreceptorsites.Itisalsotheneurotransmitterthatallowsbearsandotheranimalsto
hibernate.Consider:Heroinslowsheartrate,respiration,andmetabolismingeneralexactlywhatyou
wouldneedtohibernate.Ofcourse,sometimesheroinslowsitalldowntonothing:Permanenthibernation.

Copyright2003,2009,C.GeorgeBoeree

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