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Neurotransmitters

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http://archive.ck12.org/ck12/images?id=334457

Nervous System

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Neuron

http://springvisualculture1b.blogspot.com/2010/04/neuron-psychologist.html

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NeurotransmitterA chemical substance that is

• Synthesized in a neuron.

• Stored in presynaptic nerve terminal.

• Released into synaptic cleft.

• Act upon the postsynaptic neuron,

muscle or organ.

Axon terminal

Presynaptic membrane

Stored neurotransmitter

Synaptic cleft

Postsynaptic membrane

Synthesis of

neurotransmitter

Postsynaptic membrane receptors

Effect specific to target tissue

Axon of a neuron

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Classification of Neurotransmitters Type of Substance Examples

Ester Acetylcholine

Amino acids

Glycine

Gamma amino butyric acid (GABA)

Glutamate

Aspartate

Amines

CatecholaminesEpinephrine (Adrenaline)

Norepinephrine (Noradrenaline)Dopamine

IndolaminesSerotonin

HistamineTaurine

Peptides Endorphins, enkephalins, substance P, cholecystokinin

Others ATP, NO, CO

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Functional ClassificationFunction Examples

Excitatory(leads to depolarization )

GlutamateAspartateSerotoninHistamineATP, CO

Inhibitory(leads to hyperpolarization )

GlycineGamma amino butyric acid (GABA)

Taurine

Excitatory & Inhibitory(leads to depolarization and

hyperpolarization depending on type of receptor )

AcetylcholineEpinephrine (Adrenaline)DopamineNorepinephrine (Noradrenaline)NOEndorphins, enkephalins, substance P, cholecystokinin

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Acetylcholine• Synthesized from acetyl CoA and choline.

• Stored in presynaptic terminal

• Released into synaptic cleft

• Act upon the postsynaptic receptors

• Receptors are two types

1. Muscarinic, 2.Nicotinic

• Acetylcholine esterase hydrolyzes

acetylcholine.

Acetyl CoA

+

Choline

Effect specific to target tissue

1.Muscarinic 2.Nicotinic

Acetylcholine esterase

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Types of Cholinergic Receptors

http://www.nature.com/npp/journal/v37/n1/images/npp2011199f2.jpg

Acetylcholine Acetylcholine

Muscarinic Nicotinic

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Types of Cholinergic Receptors

Receptor Type

Natural Stimulators

Location of receptors Mechanism of action

Muscarinic 1.Ach2.Muscarine

• CNS (M1-M5)• Secretory glands e.g., Salivary,

stomach & Sweat glands (M1)• Cardiac tissue (M2)• Smooth muscles (M3)• Parasympathetic system

• M1, M3 & M5 activation of phospholipase C IP3 & DAG generation increased calcium • M2 & M4 inhibition of

adenylate cyclase decreased cAMP

Nicotinic 1.Ach2.Nicotine

CNSNeuromuscular junctionAutonomic gangliaAdrenal medulla

Activation of nicotinic receptors opening of Na+ and K+ channels depolarization

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Distribution of Cholinergic Receptors

CNS

ACh AChNic

ACh

ACh Nic NE

ACh

ACh Nic ACh

Muscarinic Parasympathetic

Nictinic: Adrenal medulla

Adrenergic: Heart and blood vessels

Muscarinic:Sweat glands

Nicotinic: Skeletal muscles

Sympathetic

Somatic

Peripheral Nervous System

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Myasthenia Gravis

http://jama.ama-assn.org/content/vol293/issue15/images/medium/jpg0420f1.jpg

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2

Epinephrine

Norepinephrine

Dopamine

Catecholamines

HH

2

http://website.lineone.net/~dave.cushman/epipen.html

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Catecholamines are derivatives of tyrosine &

contain a catechol (dihydroxybenzene) ring.

The difference between epinephrine and

norepinephrine: one additional methyl group in

structure of epinephrine.

The difference between norepinephrine and

dopamine: one additional hydroxyl group in the

structure of norepinephrine.

(Adrenaline)

(Noradrenaline)

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Sympathetic SystemSympathetic Nervous System:

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Thoracolumber Noradrenaline

Ganglion

Preganglionic nerve fibers

Postganglionic nerve fibers

ACh

Thoracic

Adrenal Medulla:

Vasoconstriction

Vasodilation

ACh

Adrenal Medulla

Adrenaline

Blood

Noradrenaline

Digestive system

Skeletal muscle

Target tissue

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Synthesis of

Adrenaline & Noradrenaline

Effect specific to target tissue

Synthesis of Adrenaline and Noradrenaline

Adrenal Medulla

Phenylalanine Hydroxylase

Tyrosine Hydroxylase

Dopamine Hydroxylase

DOPA decarboxylase

Phenylethanolamine N-Methyltransferase

Sympathetic Nerve

Synthesis of

Adrenaline & Noradrenaline

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Mechanism of Action

http://www.sp.uconn.edu/~bi107vc/images/anim/SigtranRA.gif

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Adrenergic Receptor

Alpha Beta

Alpha 1 Alpha 2 Beta 1 Beta 2

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Beta 3

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Adrenergic receptors are seven-pass transmembrane proteins.

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Mechanism of Action

http://withfriendship.com/images/c/14666/Adrenergic-receptor-wallpaper.gif

Gαβ

β

Giα GqαGsα

• These are called G protein-coupled

receptors (GPCRs).

• The three subunits are: Gα, Gβ, Gγ

• Gα carries the binding site for the

nucleotide and is different in different

types of G proteins Gs, Gi and Gq.

• Gβ and Gγ are same in all types of G proteins.

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Receptor type Tissue location

1 Arterioles (coronary, visceral, cutaneous), veins, internal sphincters, Iris dilator muscle.

2 Presynaptic membrane, pancreas, veins, adipose tissue, GIT sphincters, salivary glands.

1 Heart (SA node, atrial muscle, AV node, ventricles), kidney(JG apparatus), Adipose tissue.

2 Arterioles(muscular), veins, bronchi (muscles), liver, pancreas, uterus , Iris constrictor muscle.

3 Adipose tissue, urinary bladder.

Distribution of Adrenergic Receptor

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PIP2

IP3

DAG

Ca2+ cAMP

= Adrenaline & Noradrenaline

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1 GsGiGq

Phospholipace CAdenylate cyclase Adenylate cyclase

• Glycogen breakdown• Smooth muscle relaxes• Cardiac muscle contracts

cAMP

Smooth muscle Contraction

Ca2+

Inhibition of neurotransmitter release from neuron

Smooth muscle Contraction

Effector cell

Increased Decreased IncreasedDecreased

2

= leading to = inhibits

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↑ heart rate

↑ conduction velocity

↑contractility ↑ rate of myocyte relaxation

http://bioserv.fiu.edu/~walterm/fund_sp2004/heart/f12-20_baroreceptor_and_c.jpg

Sympathetic Nerves

Parasympathetic Nerves (Vagus)

21 M2

AChNE

+_

http://www.cvphysiology.com/Blood%20Pressure/BP010.htm

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& Norepinephrine

Cardiomyocyte

Effect of Autonomic NS on Heart

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E = Epinephrine

At low epinephrine concentrations, the beta-2

adrenergic receptors will be occupied because

these receptors have a higher affinity for

epinephrine.

At high epinephrine concentrations, the alpha-1 adrenergic

receptors will be occupied too. Because there are more

alpha-1 receptors the predominant effect at high epinephrine

concentration is vascular smooth muscle contraction.

Distribution of Adrenergic Receptor

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Dopamine

http://it.wikipedia.org/wiki/File:Dopamine_chemical_structure.png

Dopamine

Precursor Phenylalanine

Site of synthesis CNS, heart, pulmonary artery, kidney.

Receptor D1-D5 (G-protein coupled)

Effect Excitatory (D1), Inhibitory (D2). Involved in movement, cognition,

pleasure, and motivation

Disease Decreased levels leads to Parkinson’s Disease and high levels are observed in schizophrenia.

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Glycine

Glycine

Precursor Serine

Site of synthesis CNS

Receptor Glycine-A & B, NMDA

Effect Excitatory: motor function

http://o.quizlet.com/i/I8RJX-RlIpAe58vmHdpL0w_m.jpg

NMDA=N-methyl-D-aspartate

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Aspartic Acid

Aspartate

Precursor Oxaloacetate

Site of synthesis CNS

Receptor NMDA receptors

Effect Excitatory: Learning and memory.

L-Aspartate

http://0.tqn.com/d/chemistry/1/7/V/V/1/L-aspartic_acid.png

NMDA=N-methyl-D-aspartate

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Glutamate

Glutamate

Glutamate

Precursor -ketoglutarate

Site of synthesis CNS

Receptor AMPA, NMDA, kainate, metabotropic

Effect Excitatory: include cognition, memory and learning.

AMPA = amino-methyl propanoic acid

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-aminobutyric acid (GABA)

Glutamate decarboxylase

Glutamate-aminobutyric acid

(GABA)

Synthesis:

CO2

GABA

Precursor Glutamate

Site of synthesis CNS

Receptor GABA-A & B

Effect Inhibitory: include cognition, memory and learning.

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Hydroxylation & decarboxylation

Tryptophan Serotonin (5-hydroxytryptamine)

Synthesis:

Serotonin

Precursor Tryptophan

Site of synthesis Intestinal mucosal cells, CNS

Receptor 5HTA-F

Effect Excitatory: include pain perception, regulation of sleep, appetite, temperature, blood pressure, cognitive functions & mood.

Disease Decreased levels leads to some types of depression.

Serotonin

http://www.wormatlas.org/neurotransmitterstable.htm

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Histamine

Histidine

Histamine

Histamine

Precursor Histidine

Site of synthesis CNS, basophils, mast cell

Receptor H1-H4

Effect Excitatory:, sleep regulation, smooth muscle constriction, (acid secretion by stomach & immune system).

Disease Low levels in CSF in Schizophrenia.

http://web.campbell.edu/faculty/nemecz/323_lect/Nitrogen_metabolism/images/histamine.jpg

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Neuropeptides

Neuropeptides

Precursor Amino acids form large peptide which are cleaved to form short peptides.

Examples -Endorphins, Met- enkephalins, Somatostatin, Substance P, CCK etc.

Site of synthesis CNS, ANS, GIT (mainly)

Receptor G- protein coupled seven helical transmembrane proteins

Effect Excitatory & inhibitory: hunger, thirst, pleasure, pain, learning & memory.

There are around 200 neuropeptides identified.

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Miscellaneous Neurotransmitters• ATP:

– Is found in both the CNS and PNS

– Produces excitatory or inhibitory responses depending on receptor type.

– Induces Ca2+ wave propagation in astrocytes

– Provokes pain sensation

• Nitric oxide (NO) :

– Activates the intracellular receptor guanylyl cyclase

– involved in learning and memory.

• Carbon monoxide (CO):

– a main regulator of cGMP in the brain

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Subhan Allah