Autonomic Nervous System

Transcription

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2 ANS..???

3 Autonomic Nervous System

4 Nervous system CNS PNS Autonomic Somatic Symp Parasymp Enteric

5 SOMATIC AUTONOMIC Organ supplied Skeletal muscle Other organs Distal most synapse Nerve fibre Peripheral plexus Formation Within CNS Myelinated Absent Outside CNS Preganglionic - myelinated Post ganglionic non myelinated Present Efferent transmitter Ach Ach, NA Effect of nerve section on organ supplied Paralysis and Atrophy Activity maintained : no atrophy

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7 Differences between sympathetic and parasympathetic systems Sympathetic Parasympathetic Origin Dorso- lumbar Cranio sacral Distribution Wide Limited to head, neck,trunk Ganglia Away from organs On or close to organs Pre: post ganglionic fibre ratio 1:20 1:1 Postganglionic fibres Long Short Transmitter Na (major) Ach (minor) Ach

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9 Neurohumoral transmission

10 Nerves transmit their message across synapses and neuroeffector junctions by release of humoral (chemical) messengers

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12 Otto Loewi Vagusstuff of Dale 1926 Vagusstuff was Ach

13 A neurotransmitter should possess following features It should be present in the presynaptic neurons It should be released following the nerve stimulation Its application produces responses similar to those produced by nerve stimulation Its effect should be blocked or potentiated by the substance which similarly alter the effect of nerve stimulation

14 STEPS IN NEUROHUMORAL TRANSMISSION Impulse conduction Transmitter release Action on the postjunctional membrane Postjunctional activity Termination of transmitter action

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19 ????

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21 Adrenaline

22 Adrenergic System & Drugs Dr Satyajit

23 Catecholamines????

24 Catechol 1,2 dihydroxybenzene

25 Most abundant endogenous catecholamines Adrenaline / Epinephrine Noradrenaline / Norepinephrine Dopamine

26 Adrenaline Dopamine Noradrenaline

27 Noradrenaline post ganglionic sympathetic sites (sweat glands, hair follicles) Adrenaline Adrenal medulla, transmitter in brain Dopamine Major transmitter in basal ganglia, limbic system, CTZ, anterior pituitary

28 Synthesis of catecholamines

29 Hydroxylase Phenylalanine Tyrosine Liver Hydroxylase DOPA Adrenal neuronal cytoplasm Decarboxylase Dopamine ß Hydroxylase Inside granules Noradrenaline Methyl transferase Adrenaline Adrenal medulla cells

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31 Synthesis of NA/NE occurs in??? Adrenaline occurs only in??

32 Storage of catecholamines

33 Noradrenaline Synaptic vesicles within adrenergic nerve endings Vesicular membrane actively takes DA Dopa decarboxylase NA forms a complex with ATP (4:1) Adsobed to chromagranin

34 Adrenaline In adrenal medulla, NA is diffused to cytoplasm Methylation N methyl transferase NA > Adrenaline

35 Release of catecholamines

36 Release of CA occur by exocytosis All components (NA, Adr, ATP,dopamine hydroxylase) Co transmitters Indirectly acting sympathomimetic???

37 Displace NA from nerve binding site Exchange diffusion by NET

38 Uptake of catecholamines

39 Axonal Uptake Uptake 1 Active amine pump (NET) Transports NA by Na + coupled mechanism Takes NA more than Adr Most important in terminating action of NA Inhibited by Cocaine, desipramine

40 Vesicular uptake VMAT 2 (vesicular monoamine transporter) Transports NA from cytoplasm to vesicles Exchange with H + ion Takes dopamine for synthesis of NA Maintain the conc of NA Inhibited by reserpine

41 Uptake 2 Extra neuronal uptake Extra neuronal amine transporter (ENT), OCT Take Adr more than NA Not Na + dependent Not inhibited by Cocaine No pharmacological importance

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43 Metabolism of catecholamines

44 DOPGAL : 3,4 dihydroxyphenylglycolaldehyde DOPEG: 3,4 dihydroxy phenylethylene glycol DOMA: 3,4 dihydroxy mandelic acid MOPEG : 3 methoxy 4 hydroxy phenylethyleneglycol

45 Excretion Metabolites excreted in urine is VMA, MOPEG, DOMA Mostly conjugated with glucuronic acid or sulfate before excretion Only 2 5 mic gm of Adr and mic of NA excreted in free form in 24 hrs

46 Adrenergic receptors

47 Raymond Ahlquist, 1948

48 2 types Types of Adreno receptors α receptors ß receptors

49 Membrane bound GPCR Increase or decrease the camp or IP 3 /DAG Operates K + or Ca + channel

50 α ß Order of potency of agonist Adr NA >Iso Iso > Adr >NA Antagonist Phenoxybenazmaine Propranolol Effector pathway IP/DAG 3 camp, K+ channel camp, Ca+ channel

51 Beta receptor ß Organ specificity of agonist and antagonists ß1 ß2 ß3

52 Beta receptor ß1 Heart JG cells of kidney Agonist Dobutamine Selectivity : Adr = NA ß1 Cardiac stimulation, rate, force and conduction

53 Beta receptor ß2 Smooth muscle : bronchus GU, Intestine Uterus Urinary tract Eye Agonist : salbutamol, terbutaline Selectivity : Adr > NA

54 ß2 Bronchodilatation ß2 Relaxation

55 ß2 Relaxation

56 Beta receptor ß3 Adipose tissue Affinity : NA Agonist antiobesity drugs

57 Alpha receptor α α 1 α 2 α 3 α 1A, α 1B, α 1D α 2A, α 2B, α 2C

58 Alpha receptor α1 Post junctional effector organ Vasoconstriction GU smooth muscle contraction Gland secretion Gut relaxation Agonist: Phenylephrine Antagonist Prazosin

59 α 1

60 Alpha receptor α2 Pre junctional nerve endings (α2a) Post junctional Brain, pancreatic beta cells Inhibition of transmitter release Decrease central sympathetic outflow Decrease insulin release Agonist: Clonidine Antagonist Yohimbine

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62 Organ αaction ß action Blood vessels Constriction (α1) Dilatation (ß2) (arterioles and veins) Heart Little action Stimulation (ß1) Eye Radial muscle (α1) No effect Intestine Relaxation Relaxation Uterus Contraction Relaxation Splenic capsule Contraction relaxation

63 Dopamine receptors

64 Remember.. Catecholamine Adrenoreceptors

65 Thank you