Introduction to Autonomic nervous system

Neurotransmitter Chemical substance released from nerve ending, carries impulses across synapses Combines and stimulates receptors Main neurotransmitters in ANS are: Acetylcholine Noradrenaline, dopamine 11/17/2018 11/17/2018 2

Autonomic drugs Autonomic drugs: mimic or block actions of neurotransmitters Modify functions of the ANS by stimulation or blockade Have useful effects 11/17/2018 11/17/2018 3

The nervous system CNS: Peripheral NS: Brain Spinal cord Somatic nerves Autonomic nervous system (ANS) Parasympathetic system Sympathetic system Enteric nervous system 11/17/2018 11/17/2018 4

Autonomic nervous system Autonomous Not under conscious control Controls visceral involuntary functions: Heart, smooth muscle Digestion Exocrine gland functions Bladder and bowel action Necessary to maintain life 11/17/2018 11/17/2018 7

The ANS Consists of: Sympathetic system (Thoraco-lumbar) Parasympathetic system (Cranio-sacral) Enteric nervous system 11/17/2018 11/17/2018 8

Anatomy of ANS ANS consists of: Medullary centers Pregangiolinic fibers Ganglia Postganglionic fibers 11/17/2018 11/17/2018 9

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Parasympathetic system Preganglionic fibers leave with cranial nerves (3rd oculomotor, 7th facial, 10th vagus nerves) & 3rd – 4th sacral spinal nerves Ganglia in wall of end organs From ganglia post-ganglionic fibers run to innervated tissues 11/17/2018 11/17/2018 12

Sympathetic system Preganglionic fibers leave CNS through thoracic and lumbar spinal nerves Ganglia in the paravertebral chains From ganglia, post-ganglionic fibers run to innervated tissues 11/17/2018 11/17/2018 13

Functions of ANS Regulates involuntary visceral functions: Heart, SM, digestion, exocrine glands Sympathetic stimulation: Stress (physical or emotional), trauma, hypoglycaemia Lead to fight or flight response: Increase heart rate, ABP, Blood flow PS opposes sympathetic function PS regulates digestion, bladder, bowel function 11/17/2018 11/17/2018 14

Functional divisions within the nervous system

Enteric Nervous System (ENS) Collections of neurons in wall of the GIT 3rd division of the ANS Includes: Myenteric Auerbach plexus Submucosal Meissner plexus Regulates motor & secretory functions of GIT 11/17/2018 11/17/2018 20

ENS ENS contains: Cholinergic fibers Adrenergic fibers Nonadrenergic noncholinergic (NANC) neurons 11/17/2018 11/17/2018 21

NANC neurons Motor & sensory neurons in autonomic target organs (gut, bronchi & bladder) Neurotransmitters: Neuropeptides Substance P VIP (vasoactive intestinal Plypeptide) Capsaicin (of chilli peppers) releases neurotransmitters from these neurons 11/17/2018 11/17/2018 22

Neurotransmitters of the ANS Acetylcholine: on cholinergic receptors Noradrenaline: on adrenergic receptors Dopamine: on dopaminergic receptors Other neurotransmitters as: Neuropeptides Substance P VIP 11/17/2018 11/17/2018 23

Cholinergic Transmission Acetylcholine is the neurotransmitter Acts on cholinoceptors present in: Autonomic ganglia (sympathetic & parasympathetic) Postsynaptic fibers of parasympathetic system Adrenal medulla NMJ endplates 11/17/2018 24

Pathway of Acetylcholine: Synthesis: Choline is transported actively into cholinergic nerve terminals CAT Acetyl-Co A + choline Ach Choline acetyltransferase 11/17/2018 25

Pathway of Acetylcholine Storage: Ach is transported from cytoplasm into storage vesicles Protected from degradation 11/17/2018 28

Pathway of Acetylcholine Release: Action potential: Depolarization of nerve terminal Influx of calcium ions into nerve terminal Increase intra-neuronal calcium Fusion of storage vesicles with membrane Expulsion & release of Ach (exocytosis) 11/17/2018 11/17/2018 29

Pathway of Ach in the body Binding: Ach binds to & activates cholinoceptors On post-synaptic & pre-synaptic membranes Leading to various actions 11/17/2018 11/17/2018 30

Pathway of Acetylcholine Degradation Ach esterase Ach choline + acetate Very rapid Cholinesterase: in cholinergic synapses & RBC: Specific for Ach Pseudocholinesterase in plasma & liver: Not specific for Ach 11/17/2018 11/17/2018 31

Pathway of Acetylcholine Recycling: Recycling of choline back into neurons occurs to synthesis new Ach. 11/17/2018 11/17/2018 32

Inhibitors of Ach Pathway Inhibitors of release: Botulinum toxins: Botulism food poisoning Respiratory paralysis. Inhibitors of binding of ACh: Anti-cholinergic drugs. 11/17/2018 11/17/2018 33

Cholinoceptors Muscarinic receptors. Nicotinic receptors. 11/17/2018 34

Muscarinic receptors: M1 CNS Excitatory M1 Parietal cells Gastric secretion M2 Myocardium Rate, contractility, CO M2 CNS Inhibitory 11/17/2018 36

Cholinoceptors M3 Vascular SM Relaxation M3 Endothelium Nitric oxide (EDRF) M3 Circular M of iris Miosis M3 Exocrine & GIT Increase secretions M3 GIT & Bladder wall Contraction M3 GIT, Bladder sphincters Relaxation M3 Bronchi Bronchoconstriction 11/17/2018 37

Other muscarinic receptors In corpora cavernosa of penis Leading to erection through: Release of nitric oxide causing vasodilatation M4 & M5 in CNS (not well defined) 11/17/2018 38

Nicotinic receptors Nicotinic NN Autonomic ganglia (Stimulation) Nicotinic NN Adrenal medulla (Adrenaline, NA release) Nicotinic NM NMJ endplates (Muscle contraction) 11/17/2018 39

Adrenergic Drugs Neurotransmitters in adrenergic neurons are: NA & dopamine Sympathomimetics: Mimic actions of sympathetic system Derivatives of phenylethylamine Chemical modification results in various agents 11/17/2018 40

Pathway of catecholamines in the body Binding: Released NA binds with adrenoceptors: post-synaptically & pre-synaptic 11/17/2018

Termination of actions of NA Reuptake 1 into nerve terminals (Main) Reuptake 2 into post-synaptic membrane Diffusion of NA into circulation Enzymatic transformation by: MAO & COMT 11/17/2018

Enzymatic transformation Monoamine oxidase (MAO): In mitochondria of nerve terminals, intestinal mucosa & liver Catechol-O-methyl transferase (COMT): In cytoplasm of liver, lung, brain 11/17/2018

Locations & Functions of adrenoceptors in the body Alpha-adrenoceptors (-Receptors): Two main subtypes: 1: post-synaptic 2: Pre-synaptic (Nerve ending) Post-synaptic in certain sites In platelets 11/17/2018

1-Adrenoceptors Vascular SM Vsoconstriction Radial M. of iris Mydriasis Bladder sphincter Contraction Intestine sphincter Contraction Male sex organs Ejaculation Inhibits K entry into cells Hyperkalemia 11/17/2018

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2-adrenoceptors Presynaptic Control NA release - ve feedback inhibition CNS Inhibitory Platelets Enhance aggregation Islet cells pancreas Inhibit insulin secretion 11/17/2018

Beta-adrenoceptors (-receptors) 3 subtypes of -adrenoceptors: 1 Heart: Increase rate, contractility Increase automaticity & conductivity 1 Kidneys: Increase renin 11/17/2018

2-adrenoceptors Bronchi Bronchodilatation Bladder wall Relaxation Intestine wall Relaxation Skeletal M. arterioles Vasodilatation Glycogenolysis Increase blood glucose Gluconeogenesis Increase blood glucose Uterus Relaxation Skeletal muscles Tremor 11/17/2018

 -receptors 2: Mast cells Inhibits autacoid release K entry into cells Hypokalemia 3: Post-synaptic in lipocytes Lipolysis 11/17/2018