Neurotransmitters 2

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    Classification of

    Neurosecretionsneurotransmitters are released into the

    synaptic cleftin order to influenceneighboringcells. They have a short rangeand a shortlifespan.

    neurohormones are releasedinto the blood,

    allowing them to cover larger distances.

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    The sequence of events that lead topostsynaptic changes is as follows:

    The action potential signal arrives at the axonterminal The local depolarization causesCa2+ channels to open.

    Ca2+ enters the presynaptic cell because itsconcentration is greater outside the cell thaninside.The Ca2+, by binding with calmodulin,

    causes vesicles filled with neurotransmitter tomigrate towards the presynaptic membrane.

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    The vesicle merges with the presynapticmembrane.The presynaptic membrane andvesicle now forms a continuous membrane, so

    that the neurotransmitter is released into thesynaptic cleft. This process is calledexocytosis.

    The neurotransmitter diffuses through the

    synaptic cleft and binds with receptor channelmembranes that are located in bothpresynaptic and postsynaptic membranes.

    The time period from neurotransmitterrelease to receptor channel binding is lessthan a millionth of a second.

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    Direct and Indirect Binding toPostsynaptic Receptor

    There are two kinds of receptor channels:direct and indirect

    Direct: the receptor channel allows ions topass through the membrane. Theneurotransmitter acts like a key which opensthe ion channel. This is the fastest kind of

    channel (about 0.5 ms). This is called anionotropic receptor.

    http://www.columbia.edu/cu/psychology/courses/1010/mangels/neuro/glossary.htmlhttp://www.columbia.edu/cu/psychology/courses/1010/mangels/neuro/glossary.html
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    Indirect: the binding of neurotransmitter tothe receptor channel causes the release of amolecule, called a secondary messenger, thatindirectly activates nearby ion channels. Thisis called a metabotropic receptor.This process is much slower than direct receptor

    ion channels: from 30 ms up to 1 second.

    However, this is the most common type ofpostsynaptic receptor channel

    http://www.columbia.edu/cu/psychology/courses/1010/mangels/neuro/glossary.htmlhttp://www.columbia.edu/cu/psychology/courses/1010/mangels/neuro/glossary.html
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    Acetylcholine

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    Biogenic Amines

    Biogenic amines arise from amino acids bydecarboxylation.

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    Biogenic Amines

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    Synthesis of Catecholamines

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    The neurological disorder Parkinsonsdisease is associated with anunderproduction of dopamine, and it hastraditionally been treated by administering L-dopa.

    Overproduction of dopamine in the brain maybe linked to psychological disorders such asschizophrenia

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    Degradation of Catecholamines

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    Serotonin

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    Biological functions of serotonin:-

    1- It acts as excitatory chemical transmitter inthe brain where it stimulates brain activityand affects behavior. It stimulates release ofprolactin.

    2- It is present in the mast cells and platelets.It mediates platelet aggregation.

    3- It causes smooth muscle contractions in thearterioles (vasoconstriction) and bronchioles.

    4- It acts as a transmitter in GIT to releasepeptide hormones.

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    Catabolism of serotonin:-

    Oxidative deamination of serotonin bymonoamine oxidase will form 5-hydroxyindole acetic acid (5 HIAA) (normal

    value 2-8 mg/ 24 hour urine).

    The level of serotonin in the brain controls

    the mood. An increase in serotonin will causeeuphoria while its decreased level will causedepression.

    In depression, we can give a drug that inhibits

    monoamine oxidase enzyme to prevent the

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    Melatoninis a hormone, derived from tryptophan,

    serotonin is an intermediate. Melatonin isformed in the pineal body tissue and in

    peripheral nerves and secreted into the bloodand CSF.

    Melatonin is synthesized in human during thedark period of the day and maintained at alow level during the day light.

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    This diurnal variation is brought about bynorepinephrine that stimulates pineal cells tosynthesize melatonin. Norepinephrine

    increases cAMP which increases N-acetyltransferase activity.

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    GABA

    The amino acid derivative, -aminobutyrate(GABA) is a well-known inhibitor ofpresynaptic transmission in the CNS, and also

    in the retina.

    The formation of GABA occurs by the

    decarboxylation of glutamate catalyzed byglutamate decarboxylase (GAD). GAD ispresent in many nerve endings of the brain aswell as in the -cells of the pancreas. The

    activity of GAD requires pyridoxal phosphatePLP as a cofactor.

    http://themedicalbiochemistrypage.org/vitamins.htmlhttp://themedicalbiochemistrypage.org/vitamins.html
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    GABA is degraded by GABA aminotransferaseto succinate semialdehyde that is convertedto succinate.

    Theunderproduction of GABA occurs due to

    GAD or vitamin B6 deficiency, it is associatedwith epileptic seizures

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    Histamine

    It is synthesized by decarboxylation ofhistidine.

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    - Alanine

    It is synthesized by decarboxylation ofaspartic acid.

    - It is a component of carnosine andpantothenic acid.

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    Peptides

    Peptidesmake up the largest group amongthe neurosecretions. Many peptide hormones

    e. g. angiotensin IIsimultaneously act astransmitters.

    Most neuropeptides are small (315 AA).

    Endorphins, and enkephalinsare aparticularly interesting group ofneuropeptides.They act as endogenousopiates byproducing analgesic, sedative,

    and euphorianteffects in extreme situations.

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    Purine derivatives

    Purine derivativeswith neurotransmitterfunction are all derived from adenine-containing nucleotides or nucleosides. ATP is

    released along with acetylcholine and othertransmitters, and among other functions itregulates the emission of transmitters from itssynapse of origin.

    The stimulatory effect of caffeineis mainlybased on the fact that it binds to adenosinereceptors.

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