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Neurotransmitters Bibi Kulsoom.

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Presentation on theme: "Neurotransmitters Bibi Kulsoom."— Presentation transcript:

1 Neurotransmitters Bibi Kulsoom

2 Nervous System

3 Neuron

4 Neurotransmitter A 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. Synthesis of neurotransmitter Axon of a neuron Stored neurotransmitter Presynaptic membrane Axon terminal Postsynaptic membrane Synaptic cleft Postsynaptic membrane receptors Effect specific to target tissue

5 Classification of Neurotransmitters
Type of Substance Examples Ester Acetylcholine Amino acids Glycine Gamma amino butyric acid (GABA) Glutamate Aspartate Amines Catecholamines Epinephrine (Adrenaline) Norepinephrine (Noradrenaline) Dopamine Indolamines Serotonin Histamine Taurine Peptides Endorphins, enkephalins, substance P, cholecystokinin Others ATP, NO, CO

6 Functional Classification
Examples Excitatory (leads to depolarization ) Glutamate Aspartate Serotonin Histamine ATP, CO Inhibitory (leads to hyperpolarization ) Glycine Gamma amino butyric acid (GABA) Taurine Excitatory & Inhibitory (leads to depolarization and hyperpolarization depending on type of receptor ) Acetylcholine Epinephrine (Adrenaline) Dopamine Norepinephrine (Noradrenaline) NO Endorphins, enkephalins, substance P, cholecystokinin

7 Acetylcholine esterase
Synthesized from acetyl CoA and choline. Stored in presynaptic terminal Released into synaptic cleft Act upon the postsynaptic receptors Receptors are two types Muscarinic, Nicotinic Acetylcholine esterase hydrolyzes acetylcholine. Acetyl CoA + Choline Acetylcholine esterase Muscarinic 2.Nicotinic Effect specific to target tissue

8 Types of Cholinergic Receptors
Muscarinic Nicotinic Acetylcholine

9 Types of Cholinergic Receptors
Receptor Type Natural Stimulators Location of receptors Mechanism of action Muscarinic 1.Ach 2.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 2.Nicotine CNS Neuromuscular junction Autonomic ganglia Adrenal medulla Activation of nicotinic receptors  opening of Na+ and K+ channels  depolarization

10 Distribution of Cholinergic Receptors
CNS Peripheral Nervous System ACh Nic ACh Muscarinic Parasympathetic ACh Nictinic: Adrenal medulla Sympathetic ACh Nic NE Adrenergic: Heart and blood vessels ACh Nic ACh Muscarinic: Sweat glands ACh Nicotinic: Skeletal muscles Somatic

11 Myasthenia Gravis

12 kulsoom Catecholamines Epinephrine 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) Norepinephrine (Noradrenaline) 2 Dopamine H 2

13 Sympathetic System Sympathetic Nervous System: Adrenal Medulla:
kulsoom Sympathetic System Sympathetic Nervous System: Postganglionic nerve fibers Preganglionic nerve fibers Thoracolumber ACh Noradrenaline Target tissue Ganglion Vasodilation Blood Adrenal Medulla: Skeletal muscle Adrenaline Thoracic ACh Noradrenaline Adrenal Medulla Digestive system Vasoconstriction

14 Synthesis of Adrenaline and Noradrenaline
Adrenal Medulla Synthesis of Adrenaline & Noradrenaline Phenylalanine Hydroxylase Synthesis of Adrenaline & Noradrenaline Effect specific to target tissue Sympathetic Nerve Tyrosine Hydroxylase DOPA decarboxylase Dopamine Hydroxylase Phenylethanolamine N-Methyltransferase

15 Mechanism of Action

16 Adrenergic receptors are seven-pass transmembrane proteins.
kulsoom Adrenergic Receptor Alpha Beta kulsoom Alpha 1 Alpha 2 Beta 1 Beta 2 Beta 3 Adrenergic receptors are seven-pass transmembrane proteins.

17 Mechanism of Action 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. β β Giα Gsα Gqα G proteins are so-called because they bind the guanine nucleotides, GDP and GTP. They are heterotrimers (i.e., made of three different subunits) associated with the inner surface of the plasma membrane and transmembrane receptors of hormones. These are called G protein-coupled receptors (GPCRs). The three subunits are: Gα,. 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. Gβ and Gγ are same in all types of G proteins.

18 Distribution of Adrenergic Receptor
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.

19 = Adrenaline & Noradrenaline
kulsoom = Adrenaline & Noradrenaline 1 Gq 2 Gi Gs Phospholipace C Adenylate cyclase Adenylate cyclase PIP2 DAG IP3 Ca2+ Ca2+ Decreased cAMP Increased cAMP Increased Decreased Inhibition of neurotransmitter release from neuron Smooth muscle Contraction Smooth muscle Contraction Glycogen breakdown Smooth muscle relaxes Cardiac muscle contracts Effector cell = inhibits = leading to

20 Effect of Autonomic NS on Heart
Parasympathetic Nerves (Vagus) Sympathetic Nerves & Norepinephrine ACh NE 2 1 M2 ↑ heart rate ↑ conduction velocity ↑contractility ↑ rate of myocyte relaxation _ + Cardiomyocyte Kulsoom animated from

21 Distribution of Adrenergic Receptor
kulsoom Distribution of Adrenergic Receptor 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.

22 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.

23 Glycine Precursor Serine Site of synthesis CNS Receptor
Glycine-A & B, NMDA Effect Excitatory: motor function NMDA=N-methyl-D-aspartate

24 Aspartic Acid L-Aspartate Precursor Oxaloacetate Site of synthesis CNS
Receptor NMDA receptors Effect Excitatory: Learning and memory. NMDA=N-methyl-D-aspartate

25 Glutamate Precursor -ketoglutarate Site of synthesis CNS Receptor
AMPA, NMDA, kainate, metabotropic Effect Excitatory: include cognition, memory and learning. AMPA = amino-methyl propanoic acid

26 -aminobutyric acid (GABA)
CO2 Synthesis: Glutamate decarboxylase -aminobutyric acid (GABA) Glutamate GABA Precursor Glutamate Site of synthesis CNS Receptor GABA-A & B Effect Inhibitory: include cognition, memory and learning.

27 (5-hydroxytryptamine)
Serotonin Synthesis: Hydroxylation & decarboxylation Serotonin (5-hydroxytryptamine) Tryptophan 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.

28 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.

29 Neuropeptides Neuropeptides
There are around 200 neuropeptides identified. 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.

30 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

31 Subhan Allah


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