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NEUROTRANSMITTERS

Rondang Soegianto

2009

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The nervous system controls and

regulatesevery mental and physical activity

* Movement

* thought (concrete & abstract)

* Feeling

* reasoning

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Alertness = Function of CNS

Coma = Inability to respond to stimulusIncluding pain

Coma >< Alertness

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Relation of brain function to

- rational thought

- individual personality

Until now still unexplainable

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Brain functions at 2 levels

* Macroprocessor for all sensory inputand motor function

* Contains human characteristics:memory, emotion, rationality

Personality:Interface between those 2 functions

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LIMBIC System plays a key role in

EMOTION

Limbic system = Ring of forebrainstructures surrounding brain stem

interconnected by neuronal pathwaysFunctionally related with higher cortex

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Cortex provides neural mechanism forskeletal muscle activity to displayemotional expression (smiling)

Capable of consciously suppressingExternal manifestation of emotionalbehavior

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Norepinephrine !! Neurotransmitters

Dopamine ! for! Emotion &Serotonin ! Behavior

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Some neurotransmitters (NT) function thru

intracellular second-messenger system

Example:Effect of epinephrine on thesynthesis of cyclic AMP (cAMP)

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Neurotransmitters (NT)and

Neuromodulators (NM)

Synthesized in neurons.

Metabolic center of neurons called:Cell body, cyton, perikaryon

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A. Typical neuron. Transmitter releasedacross synaptic gap

B. Typical neurosecretory cell.Neurosecretion released into bloodvessel

Found in hypothalamus andpituitary cell

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No sharp distinction between NT and NM

Distinction based on synaptic activity

NT has direct effect on synaptic membrane

NM modulates or regulates action of NT

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Acetylcholine

Synthesized in synaptic terminals from

Asetyl-CoA + Phosphatidylcholine(or circulating choline)

Enzyme: Choline acetyltransferase (CAT)

CAT = marker for cholinergic synapses

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Acetil-CoA produced in mitochondria from

- Piruvate oxidative decarboxylation

- - Oxidation of fatty acids

Phosphatidylcholine abundant in biomembranes Alanine Etanolamine CholinePhosphatidyletanolamine Phosph.choline

= Lecithin

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Nicotinic ACh (nACh)- Ionotropic- Found in synapses at muscular junctions

Also present in brain

Muscarinic Ach (mACh)- Metabotropic- In brain synapses: mACh >> nACh- Coupled to G-protein- Stimulates adenilyl cyclase- Controls K+-channel

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Myasthenia Gravis

Autoimmune disease Antibodies synthesized against own

nAChReceptor complex destroyed Ach released by motor neuron terminals on

motor end plate not taken up by nAChRsMuscular weakness

Treatment: Neostigmine, inhibits AChEsterase

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AMINO ACIDS

Excitatory Amino Acids- Glutamic acid- Aspartic acid

Inhibitory Amino Acids- -Amino-butyric acid (GABA)- Glycine

Control of body movements need balancedBetween excitatory and inhibitory synapses.

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Glutamic acid and Aspartic acid =Non-essential amino acids

Synthesized in synaptic mitochondriafrom Krebs cycle componentsoxaloacetate (Asp) and -ketoglutarate (Glu)

GABA formed by decarboxylation of Glu byGlutamic acid decarboxylase

Glycine = smallest amino acidMostly restricted to spinal cord and brain stem

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Serotonin = 5-hydroxytryptamine

Formed from tryptophan- Tryptophan hydroxylase- Aromatic amino acid decarboxylase

Stored in vesiclesSequestration blocked by reserpine

Free serotonin 5- HIAA (5-OH indole ac.acic)Enzyme: MAO (monoamine oxidase)

Inhibited by Iproniazid

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CatecholaminesDopamineNorepinephrine

PurinesExternally applied ATP can cause

vasodilation, esp. coronary vasodltn

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Cannabis ( Marijuana, Hashish)Psychoactive compound extracted fromCannabis sativa Effect in brain memory loss

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Nitric oxide (NO)Formed from arginine by NO synthaseNot sequestered into vesiclesNo subsynaptic receptors

No reuptake system into presynapticreceptorsSmall molecules diffuse from site of production

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