A general account of chemical basis of signalling.

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Neurotransmitters
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Bibi Kulsoom
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Nervous System
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http://archive.ck12.org/ck12/images?id=334457
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Neuron
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http://springvisualculture1b.blogspot.com/2010/04/neuron-psychologist.html
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Neurotransmitter
A chemical substance that is
• Synthesized in a neuron.
• Stored in presynaptic nerve terminal.
Synthesis
of
neurotransmitter
Axon of a neuron
• Released into synaptic cleft.
• Act upon the postsynaptic neuron,
Stored
neurotransmitter
muscle or organ.
Presynaptic
membrane
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Axon terminal
Postsynaptic
membrane
Synaptic cleft
Postsynaptic membrane receptors
Effect specific to target tissue
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Classification of Neurotransmitters
Type of Substance
Examples
Ester
Acetylcholine
Glycine
Amino acids
Gamma amino butyric acid (GABA)
Glutamate
Aspartate
Epinephrine (Adrenaline)
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Catecholamines
Norepinephrine (Noradrenaline)
Dopamine
Amines
Serotonin
Indolamines
Histamine
Taurine
Peptides
Endorphins, enkephalins, substance P,
cholecystokinin
Others
ATP, NO, CO
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Functional Classification
Function
Examples
Glutamate
Excitatory
(leads to depolarization )
Aspartate
Serotonin
Histamine
ATP, CO
Glycine
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Inhibitory
(leads to hyperpolarization )
Excitatory & Inhibitory
(leads to depolarization and
hyperpolarization depending on type of
receptor )
Gamma amino butyric acid (GABA)
Taurine
Acetylcholine
Epinephrine (Adrenaline)
Dopamine
Norepinephrine (Noradrenaline)
NO
Endorphins, 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
Acetyl CoA
+
Choline
• Receptors are two types
1. Muscarinic,
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Acetylcholine
esterase
2.Nicotinic
• Acetylcholine esterase hydrolyzes
acetylcholine.
1.Muscarinic
2.Nicotinic
Effect specific to target tissue
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Types of Cholinergic Receptors
Muscarinic
Acetylcholine
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http://www.nature.com/npp/journal/v37/n1/images/npp2011199f2.jpg
Nicotinic
Acetylcholine
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Types of Cholinergic Receptors
Receptor
Type
Natural
Stimulators
Location of receptors
Mechanism of action
Muscarinic 1.Ach
2.Muscarine
• CNS (M1-M5)
• M1, M3 & M5 
• Secretory glands e.g., Salivary,
activation of
stomach & Sweat glands (M1)
phospholipase C 
• Cardiac tissue (M2)
IP3 & DAG generation
• Smooth muscles (M3)
 increased calcium
• Parasympathetic system
• M2 & M4  inhibition
of adenylate cyclase
 decreased cAMP
Nicotinic
CNS
Neuromuscular junction
Autonomic ganglia
Adrenal medulla
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1.Ach
2.Nicotine
Activation of nicotinic
receptors  opening of
Na+ and K+ channels 
depolarization
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Distribution of Cholinergic Receptors
Peripheral Nervous System
CNS
ACh Nic
ACh
ACh
Muscarinic
Parasympathetic
Nictinic:
Adrenal medulla
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ACh Nic
NE
ACh Nic
ACh
Muscarinic:
Sweat glands
ACh
Nicotinic:
Skeletal muscles
Adrenergic:
Heart and blood vessels
Sympathetic
Somatic
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Myasthenia Gravis
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http://jama.ama-assn.org/content/vol293/issue15/images/medium/jpg0420f1.jpg
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kulsoom
Catecholamines
Epinephrine
Catecholamines are derivatives of tyrosine &
(Adrenaline)
contain a catechol (dihydroxybenzene) ring.
The difference between epinephrine and
Norepinephrine
(Noradrenaline)
norepinephrine: one additional methyl group in
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structure of epinephrine.
2
The difference between norepinephrine and
dopamine: one additional hydroxyl group in the
structure of norepinephrine.
Dopamine
H
2
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http://website.lineone.net/~dave.cushman/epipen.html
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Sympathetic System
Sympathetic Nervous System:
Thoracolumber
Preganglionic
nerve fibers
Postganglionic
nerve fibers
ACh
Noradrenaline
Target tissue
Ganglion
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Blood
Adrenal Medulla:
Vasodilation
Skeletal muscle
Adrenaline
Thoracic
ACh
Noradrenaline
Adrenal
Medulla
Digestive system
Vasoconstriction
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Synthesis of Adrenaline and Noradrenaline
Adrenal
Medulla
Synthesis
of
Adrenaline &
Noradrenaline
Phenylalanine Hydroxylase
Tyrosine Hydroxylase
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Synthesis
of
Adrenaline &
Noradrenaline
Sympathetic
Nerve
DOPA decarboxylase
Dopamine
Hydroxylase
Phenylethanolamine
N-Methyltransferase
Effect specific to target tissue
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Mechanism of Action
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http://www.sp.uconn.edu/~bi107vc/images/anim/SigtranRA.gif
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Adrenergic Receptor
Alpha
Beta
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Alpha 1
Alpha 2
Beta 1
Beta 2
Beta 3
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Adrenergic receptors are seven-pass transmembrane proteins.
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Mechanism of Action
• These are called G protein-coupled
Gα
receptors (GPCRs).

β

β
• The three subunits are: Gα, Gβ, Gγ
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• Gα carries the binding site for the
Giα
Gsα
Gqα
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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http://withfriendship.com/images/c/14666/Adrenergic-receptor-wallpaper.gif
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Distribution of Adrenergic Receptor
Receptor type
1
Tissue location
Arterioles (coronary, visceral, cutaneous), veins, internal
sphincters, Iris dilator muscle.
2
Presynaptic membrane, pancreas, veins, adipose tissue, GIT
sphincters, salivary glands.
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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.
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= Adrenaline & Noradrenaline
1
2
Gq
Gi

Gs
Phospholipace C
Adenylate cyclase
Adenylate cyclase
PIP2
DAG
IP3
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2+
Decreased Ca
Increased Ca2+
Smooth muscle
Contraction
Decreased cAMP
Inhibition of
neurotransmitter
release from
neuron
Smooth muscle
Contraction
Increased cAMP
• Glycogen breakdown
• Smooth muscle relaxes
• Cardiac muscle contracts
Effector cell
= inhibits
= leading to
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Effect of Autonomic NS
on Heart
Sympathetic
Nerves
Parasympathetic
Nerves (Vagus)
NE
ACh
2 1
M2
& Norepinephrine
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↑ heart rate
↑ conduction velocity
+
Cardiomyocyte
↑contractility
↑ rate of myocyte
relaxation
_
http://www.cvphysiology.com/Blood%20Pressure/BP010.htm
http://bioserv.fiu.edu/~walterm/fund_sp2004/heart/f12-20_baroreceptor_and_c.jpg
Kulsoom animated from http://www.cvphysiology.com/Blood%20Pressure/BP010.htm
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Distribution of Adrenergic Receptor
E = Epinephrine
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At low epinephrine concentrations, the beta-2
At high epinephrine concentrations, the alpha-1 adrenergic
adrenergic receptors will be occupied because
receptors will be occupied too. Because there are more
these receptors have a higher affinity for
alpha-1 receptors the predominant effect at high epinephrine
epinephrine.
concentration is vascular smooth muscle contraction.
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Dopamine
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,
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pleasure, and motivation
Disease
Decreased levels leads to Parkinson’s Disease and high levels are
observed in schizophrenia.
http://it.wikipedia.org/wiki/File:Dopamine_chemical_structure.png
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Glycine
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Glycine
Precursor
Serine
Site of synthesis
CNS
Receptor
Glycine-A & B, NMDA
Effect
Excitatory: motor function
NMDA=N-methyl-D-aspartate
http://o.quizlet.com/i/I8RJX-RlIpAe58vmHdpL0w_m.jpg
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Aspartic Acid
L-Aspartate
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Aspartate
Precursor
Oxaloacetate
Site of synthesis
CNS
Receptor
NMDA receptors
Effect
Excitatory: Learning and memory.
NMDA=N-methyl-D-aspartate
http://0.tqn.com/d/chemistry/1/7/V/V/1/L-aspartic_acid.png
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Glutamate
Glutamate
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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)
CO2
Synthesis:
Glutamate
decarboxylase
Glutamate
-aminobutyric acid
(GABA)
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GABA
Precursor
Glutamate
Site of synthesis
CNS
Receptor
GABA-A & B
Effect
Inhibitory: include cognition, memory and learning.
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Serotonin
Synthesis:
Tryptophan
Hydroxylation &
decarboxylation
Serotonin
(5-hydroxytryptamine)
Serotonin
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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.
http://www.wormatlas.org/neurotransmitterstable.htm
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Histamine
Histidine
Histamine
Histamine
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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
There are around 200 neuropeptides identified.
Neuropeptides
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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.
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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
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• 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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http://myyatradiary.blogspot.com/2011/08/treks-beyond-badrinath-swargarohini.html

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