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Kuls oo m Neurotransmitters Bibi Kulsoom. Kuls oo m Nervous System.

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Presentation on theme: "Kuls oo m Neurotransmitters Bibi Kulsoom. Kuls oo m Nervous System."— Presentation transcript:

1 Kuls oo m Neurotransmitters Bibi Kulsoom

2 Kuls oo m Nervous System

3 Kuls oo m Neuron

4 Kuls oo m 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. 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

5 Kuls oo m Classification of Neurotransmitters Type of Substance Examples EsterAcetylcholine 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 Kuls oo m Functional Classification FunctionExamples 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 Kuls oo m 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.Muscarinic2.Nicotinic Acetylcholine esterase

8 Kuls oo m Types of Cholinergic Receptors Acetylcholine MuscarinicNicotinic

9 Kuls oo m Types of Cholinergic Receptors Receptor Type Natural Stimulators Location of receptorsMechanism of action Muscarinic1.Ach 2.Muscarine CNS (M 1 -M 5 ) Secretory glands e.g., Salivary, stomach & Sweat glands (M 1 ) Cardiac tissue (M 2 ) Smooth muscles (M 3 ) Parasympathetic system M 1, M 3 & M 5  activation of phospholipase C  IP3 & DAG generation  increased calcium M 2 & M 4  inhibition of adenylate cyclase  decreased cAMP Nicotinic1.Ach 2.Nicotine CNS Neuromuscular junction Autonomic ganglia Adrenal medulla Activation of nicotinic receptors  opening of Na + and K + channels  depolarization

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

11 Kuls oo m Myasthenia Gravis

12 Kuls oo m 12 2 Epinephrine Norepinephrine Dopamine Catecholamines HH 2 kulsoom 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)

13 Kuls oo m Sympathetic System Sympathetic Nervous System: kulsoom 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

14 Kuls oo m 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

15 Kuls oo m 15 Mechanism of Action

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

17 Kuls oo m 17 Mechanism of Action GαGα GαGα β β   β β   Giα Gqα Gsα 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.

18 Kuls oo m Receptor typeTissue location 11 Arterioles (coronary, visceral, cutaneous), veins, internal sphincters, Iris dilator muscle. 22 Presynaptic membrane, pancreas, veins, adipose tissue, GIT sphincters, salivary glands. 11 Heart (SA node, atrial muscle, AV node, ventricles), kidney(JG apparatus), Adipose tissue. 22 Arterioles(muscular), veins, bronchi (muscles), liver, pancreas, uterus, Iris constrictor muscle. 33 Adipose tissue, urinary bladder. Distribution of Adrenergic Receptor

19 Kuls oo m 19 PIP 2 IP 3 DAG Ca 2+ cAMP = Adrenaline & Noradrenaline kulsoom 11  GsGs GiGi GqGq Phospholipace C Adenylate cyclase Glycogen breakdown Smooth muscle relaxes Cardiac muscle contracts cAMP Smooth muscle Contraction Ca 2+ Inhibition of neurotransmitter release from neuron Smooth muscle Contraction Effector cell Increased Decreased Increased Decreased 22 = leading to = inhibits

20 Kuls oo m ↑ heart rate ↑ conduction velocity ↑ contractility ↑ rate of myocyte relaxation Sympathetic Nerves Parasympathetic Nerves (Vagus) 22 11 M2M2 ACh NE + _ Kulsoom animated from & Norepinephrine Cardiomyocyte Effect of Autonomic NS on Heart

21 Kuls oo m 21 kulsoom 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

22 Kuls oo m Dopamine Dopamine PrecursorPhenylalanine Site of synthesisCNS, heart, pulmonary artery, kidney. ReceptorD 1 -D 5 (G-protein coupled) Effect Excitatory (D 1 ), Inhibitory (D 2 ). Involved in movement, cognition, pleasure, and motivation DiseaseDecreased levels leads to Parkinson’s Disease and high levels are observed in schizophrenia.

23 Kuls oo m Glycine PrecursorSerine Site of synthesisCNS ReceptorGlycine-A & B, NMDA EffectExcitatory: motor function NMDA=N-methyl-D-aspartate

24 Kuls oo m Aspartic Acid Aspartate PrecursorOxaloacetate Site of synthesisCNS ReceptorNMDA receptors EffectExcitatory: Learning and memory. L-Aspartate NMDA=N-methyl-D-aspartate

25 Kuls oo m Glutamate Precursor  -ketoglutarate Site of synthesisCNS ReceptorAMPA, NMDA, kainate, metabotropic EffectExcitatory: include cognition, memory and learning. AMPA = amino-methyl propanoic acid

26 Kuls oo m  -aminobutyric acid (GABA) Glutamate decarboxylase Glutamate  -aminobutyric acid (GABA) Synthesis: CO 2 GABA PrecursorGlutamate Site of synthesisCNS ReceptorGABA-A & B EffectInhibitory: include cognition, memory and learning.

27 Kuls oo m Hydroxylation & decarboxylation Tryptophan Serotonin (5-hydroxytryptamine) Synthesis: Serotonin PrecursorTryptophan Site of synthesisIntestinal mucosal cells, CNS Receptor5HT A-F Effect Excitatory: include pain perception, regulation of sleep, appetite, temperature, blood pressure, cognitive functions & mood. DiseaseDecreased levels leads to some types of depression. Serotonin

28 Kuls oo m Histamine Histidine Histamine PrecursorHistidine Site of synthesisCNS, basophils, mast cell ReceptorH 1 -H 4 EffectExcitatory:, sleep regulation, smooth muscle constriction, (acid secretion by stomach & immune system). DiseaseLow levels in CSF in Schizophrenia.

29 Kuls oo m Neuropeptides PrecursorAmino acids form large peptide which are cleaved to form short peptides. Examples  -Endorphins, Met- enkephalins, Somatostatin, Substance P, CCK etc. Site of synthesisCNS, ANS, GIT (mainly) ReceptorG- protein coupled seven helical transmembrane proteins EffectExcitatory & inhibitory: hunger, thirst, pleasure, pain, learning & memory. There are around 200 neuropeptides identified.

30 Kuls oo m Miscellaneous Neurotransmitters ATP: – Is found in both the CNS and PNS – Produces excitatory or inhibitory responses depending on receptor type. – Induces Ca 2+ 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 Kuls oo m

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