NEUROTRANSMITTERS AND

NEUROMODULATION

DR SHWETHA VIJAYAN
 NEUROTRANSMITTERS

• Acetylcholine
• Amino peptides
• Amines
• Neuro-peptides
 ACETYLCHOLINE

• Found in : Cholinergic neurons

Neuromuscular junctions
Autonomic System- Autonomic ganglia, All preganglionic neurons,
All parasympathetic Postganglionic neurons.
 ACETYLCHOLINE

Acetyl Co A + choline (ECF)- enters cell through

Na- dependant mechanism.
To form Ach.
Quantal release predominantly.
Receptors – Nicotinic and Muscarinic
 ACETYL CHOLINE RECEPTORS

NICOTINIC
- Pentameric Ligand gated channels
- Present at NMJ- stimulation causes muscular
contraction
- Mature nicotinic receptor at the postsynaptic
(muscular) membrane is composed of 5
subunits (two α, and one each of β, δ, and
gamma subunits).
 NICOTINIC RECEPTOR

- These subunits are arranged in a barrel or cylindrical

shape around a central pore. Each of the two α subunits
has an acetylcholine-binding site
- Acetylcholine binds to the α subunit; both α subunits
must be bound to an acetylcholine molecule in order to
trigger conformational change of ion channel to allow
influx of calcium and sodium ions intracellularly, and to
allow efflux of potassium out of cell.
 ACETYL CHOLINE RECEPTORS

MUSCARINIC
• These receptors are seven transmembrane G-protein coupled receptors.
• There are five described subtypes of muscarinic receptors (M1-M5).
• mAChR play major role in the parasympathetic nervous system for
diverse functions, including
-regulation of smooth muscle activity,
-wakefulness,
-hormone secretion,
- heart rate.
 FUNCTIONS

• Plays a role both in the PNS and the CNS

• PNS- involved in activating muscles. Major

transmitter of the ANS.
• CNS- involved in multiple cognitive
functions, pain, recent memory,
locomotion, circadian rhythm,
thermoregulation, salivation.
 APPLICATION

• Damage of cholinergic pathways shows a huge role in memory associated

diseases- Alzheimers,
• Curare, snake poison

• Myeasthenia gravis- Myasthenia gravis is an autoimmune diseasewhich

results from antibodies that block or destroy nicotinic acetylcholine receptors
 at the junction between the nerve and muscle. This prevents nerve impulses
 from triggering muscle contractions.
 BIOGENIC AMINE TRANSMITTERS

Synthesised from amino- acids

Nor-adrenaline
Dopamine
Adrenaline
Serotonin
Histamine
 CATECHOLAMINES

• Tyrosine A hydroxylated by tyrosine

hydroxylase to form L-Dopa.

• L-Dopa decarboxylated to Dopamine

• Dopamine is beta hydroxylated to Nor-

adrenaline

• Noradrenaline is methylated in the adrenal

medulla to adrenaline.
 NORADRENALINE

• Found in :- CNS, ANS, GANGLIA, GIT, HEART

• RECEPTORS- alpha and beta.
• These are Metabotrophic G-protein coupled Receptors
• Inactivated by Mono-amine Oxidase (MAO) and Catecholamine –
Methyl- transferase (COMT)
• Active reuptake at synaptic cleft.
Can be administered- IM, IV, SC, inhalational .

Treats myriad of clinical conditions from

anaphylaxis to croup, to bronchospasm,
cardiopulmonary arrest .

Beta effects seen first before alpha- increase

contractility, heart rate , causes vasodilation .

Hence increasing blood pressure

Also called levophed.

Routinely used in ICU and pre-op settings

Increase in Blood pressure through both
alpha and beta recpetors

Used for hypotenisve patients- in shock

• ACETYL CHOLINE
• CATECHOLAMINES – EPINEPHRINE/NE. ADRENALINE / NOR
• DOPAMINE
• GABA
• GLUTAMATE
• HISTAMINE
• SEROTONIN
• ASPARTATE
• NEUROACTIVE PEPTIDES
• NEUROMODULATION
 DOPAMINE

• Found in :- CNS, ANS, GANGLIA

• RECEPTORS :- all metabotrophic G-protein- D1-D5
• Act through Cyclic AMP
• Inactivated by COMT and MAO.
• Several diseases of the nervous system - dysfunctions of the
dopamine system.
• medications used to treat them work by altering the effects of
dopamine. 
• Parkinson's disease, a degenerative condition causing tremor and
motor impairment, is caused by a loss of dopamine-secreting
neurons in an area of the midbrain 
• Its metabolic precursor L-DOPA can be
manufactured; Levodopa, a pure form of L-DOPA, is the most
widely used treatment for Parkinson's.
 SEROTONIN

• 5- hydroxytryptamine
• Found in: blood platelets,
• Brainstem, pineal gland .
• It is a mono-amine NT.
• Produced and found mostly in the GIT (90%) and the rest
in the CNS neurons.
• RECEPTORS: 5-HT1 A-D,
• 5-HT2 , 5-HT3 , 5HT4
 SEROTONIN

Functions: regulates sleep- circadian rhythm ,

appetite, memory, temperature regulation, behaviour,
muscle contraction, and function CVS and endocrine
system.

Broken down by MAO

 HISTAMINE- NT

• Synthesized from Histidine

• Found : Hypothalamus
• Receptors: metabotrophic ; H1, H2, H3.
• Bio-degraded by MAO.
• Functions: Arousal, pain threshold, pituitary regulations .
 AMINO-ACIDS AS NT

• Glutamate and Aspartate

GLUTAMATE
• Found in the CNS- Both receptors
• Predominantly Excitatory
• Receptors: ionotrophic and metabotrophic

RECEPTORS- METABOTROPHIC IONOTROPHIC

Serpentine G- coupled. Ligand-gated ion channels.
Increase IP3 and DAG AMPA or NMDA
,
Long term potentiation- major role in
memory.
 NMDA - RECEPTOR

Ca2+ flux through NMDARs is thought to be critical in synaptic plasticity,

a cellular mechanism for learning and memory.
• The activity of the NMDA receptor is affected by many psychoactive
 drugs such as phencyclidine (PCP), alcohol (ethanol) and 
dextromethorphan (DXM).
• The anaesthetic and analgesic effects of the drugs ketamine and 
nitrous oxide are partially because of their effects on NMDA receptor
activity. 
 C O N T I N U AT I ON … . .

• ASPARTATE
• Product of Krebs cycle.

• Aspartate (the conjugate base of aspartic acid) stimulates 

NMDA receptors, though not as strongly as the amino acid
neurotransmitter L-glutamate does

.
 GABA

GAMMA- AMINO BUTYRIC ACID

• Mainly an inhibitory NM.
• Receptors:
GABA A- ionotrophic, GABA B- Metabotrophic, GABA C- Metabatrophic

GABA-A- target for alcohol, sleeping pills, anaesthesia

GABA B and C- increase K conductance
 NEUROACTIVE PEPTIDES

• Proteins synthesized in Soma

• NT
• Neuromodulator

CLASSICAL VS PEPTIDE NT
Synthesis- No clearcut synthesis for peptide
Transport- proteins synthesized in soma , transported via axonal transport (FAST)
Vesicle- NT (small) Peptide (electron dense)
Release- NT (Clearcut system) Peptide (No release)
Termination- NT (enzyme) Peptide ( peptide is cleaved to another)
Action – NT Peptide- Neuromodulation