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:

• Norepinephrine
• Epinephrine
• Dopamine
• Histamine
• Serotonin

Class III – Amino Acids

• 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