NEUROTRANSMITTERS – FUNCTIONS & MECHANISM OF ACTION IN CNS

NEUROTRANSMITTERS

• Chemicals allowing transmission either between target cells/neurons across the synapse.

• Stored in secretory vesicles of pre-synaptic neurons

Types:

Classification criteria:

1. Based on structure & size of synaptic vesicles:

• Small clear vesicles:

– Acetylcholine, glycine, GABA, and glutamate

• Small vesicles with dense core:

– Catecholamine

• Large vesicles with dense core:

-Neuropeptide 

2. Based on chemical nature:

• Class I – Acetylcholine

• Class II – Amines:Class III – Amino Acids

– Norepinephrine

– Epinephrine

– Dopamine

– Histamine

– Serotonin

– Glutamate

– Glycine

– GABA

– Aspartate

• Class IV – Nitric oxide

3. Based on molecular size of neurotransmitter:

a. Small molecular transmitters:

• Acetylcholine

• Norepinephrine

• Epinephrine

• Dopamine

• Serotonin

• Glutamate

• Glycine

• GABA

• Aspartate

• Nitric oxide

b. Large molecule transmitters: 

Neuropeptides:

• Substance P

• Encephalin

• Beta-endorphins

• Hypothalamic releasing hormones

4. Classification based on mode of action:

Excitatory:

• Glutamate – Chief excitatory neurotransmitter in brain & spinal cord

• Aspartate – Chief excitatory neurotransmitter in cortical pyramidal cells

Inhibitory:

• Gamma-AminoButyric Acid (GABA)

• Major inhibitory neurotransmitter of CNS & exerts indirect inhibition.

• Glycine – Direct inhibition.

5. Classification based on receptors:

Inotropic:

• Glutamate: AMPA, Kainate, & NMDA

• GABA: GABA a type

• Acetylcholine:  Nicotinic (N m and N n)

• Serotonin: 5HT3 

Functions:

• Transmembrane ion channels

– Facilitates transport of different ions in & out of cell

– Binding of neurotransmitter either opens or closes ion channel.

– Hence, “Ligand-gated transmembrane ion channels”

Metabotropic:

• Glutamate:  mGluR (Seven types – mGluR (1 – 7)

• GABA: GABA b type 

• Acetylcholine: Muscarinic – M1 to M5 (five types)

• Norepinephrine:  Alpha & Beta receptors

• Serotonin: 5HT 1A, 5HT 1B, 5HT 1D, 5HT 2A, 5HT 2C, 5HT 4

Functions:

• G-protein coupled receptors

• Acting through second messenger

Characteristics of neurotransmitters:

Acetylcholine:

Origin: 

• Secreted by neurons in,

– Terminals of large pyramidal cells of motor cortex

– Neurons of basal ganglia

– Motor nerves innervating the skeletal muscles

Mode of action: 

• Excitatory action(Predominately)

• Combination of excitatory & inhibitory actions.

Nor-epinephrine:

Origin:

• Secreted by terminals of neurons

• With cell bodies in brainstem & hypothalamus. 

• Specific location: Locus cerulus

Mode of action:

• Combination of excitatory & inhibitory actions.

Dopamine:

• Origin: Substania nigra

• Mode of action: Inhibitory action

Glycine:

• Origin: Synapses in Spinal cord

• Mode of action: Inhibitory action

GABA:

• Origin: Nerve ending of spinal cord, basal ganglia, cerebellum, & areas of cortex.

• Mode of action: Inhibitory action

• Origin:Mode of action: Excitatory action

– Secreted by presynaptic terminals of sensory pathways entering CNS

– Cerebral cortex

Serotonin:

Origin:

• Nuclei from median raphe of brainstem

• Projecting to dorsal horn of spinal cord & to hypothalamus.

Mode of action:

• Inhibitory of pain pathways

• Actions on higher regions of nervous system

• Controls mood of a person and induce sleep.

Nitric oxide:

• Characteristic feature:

– Neither produced from the neuronal calls nor stored in vesicles

• Mode of action:

– Direct and instant action on target areas by simple diffusion

Neuropeptide transmitters:

• Origin:

– Synthesized in ribosome-golgi apparatus in neuronal cell body 

– Stored in nerve terminals

• Function: 

– Most act as a hormone eg:- ADH, Oxytocin 

Substance P:

• Released by primary pain nerve endings

• Dorsal horn of spinal cord, Hypothalamus & from nigrostrial pathway of basal ganglia.

Opioid peptides:

• Encephalin, endorphins & dynorphin

Function:

• Important role as central inhibitor of pain signals

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