The autonomic nervous system

5. The autonomic nervous system Controls smooth muscles, exocrine and some endocrine secretions, rate and force of the heart, and certain metabolic processes. Sympathetic and parasympathetic systems have opposing actions in some situations. The sympathetic stimulation occurs in stress and the actions are recovered at rest by the parasympathetic.

6. *It should be noted that the autonomic nervous system is always working. It is NOT only active during "fight or flight" or "rest and digest" situations. Rather, the autonomic nervous system acts to maintain normal internal functions and works with the somatic nervous system

7. The Sympathetic Nervous System • The preganglionic motor neurons of the sympathetic system arise in the spinal cord and pass into sympathetic ganglia which are organized into two chains that run parallel to and on either side of the spinal cord.

8. 3) Leave the ganglia by way of a cord, leading to special ganglion (e.g. the solar plexus) in the viscera. It may here synapse with post-ganglionic sympathetic neurons running to the smooth muscular wall of the viscera. 4) Some others pass to the adrenal medulla and may synapse with the highly-modified post-ganglionic cells, making the secretory portion of the adrenal medulla. (epinephrine)

9. NEUROTRANSMITTER Definition: “substance that is released at a synapse by one neuron and that affects a postsynaptic cell…in a specific manner”

10. Noradrenaline release causes Dilation of trachea and bronchi Peristalsis Heart beat Pupil dilation Liver glycogenolysis Sphincters of rectal and bladder contraction Blood Pressure

11. Parasympathetic Nervous System • The main nerves are the tenth cranial and the vagus nerves that originate in the medulla oblongata. • Other preganglionic parasympathetic nerves also extend from the brain as well as the lower tip of the spinal cord. • Each preganglionic neurone passes into few post-ganglionic neurons located near or in the effector organ; a muscle or gland.

12. Parasympathetic stimulation Returns body function to normal after sympathetic stimulation Peristalsis Heart beat Pupil constriction Blood Pressure Vagus keeps inflammation under control Lowers TNF-α production Increase blood flow to the skin and viscera

13. Transmitters of the autonomic nervous system Noradrenaline Acetylcholine All post-ganglionic sympathetic (except sweat glands) nerve fibres, acting on α and β receptors. # All motor nerve fibres (nicotinic R) # All postganglionic parasympathetic (muscarinic R) # Autonomic ganglia (nicotinic) # Adrenal medulla (nicotinic} #The post-ganglionic sympathetic supplying sweat glands (muscarinic)

16. a1-Agonist a1 Phosphatidylinositol diphosphate Ca ++ Cell Membrane Gs Phospholipase C PI3 SR DAG Ca 2+ Ca ++ -dependent protein kinase Protein kinase C

17. a2- Agonist Enzyme-PO4 No biological effect a2 Cell Membrane AC Gi ATP cAMP AC= Adenylyl cyclase

18. b -Agonist b - receptor Cell Membrane Gs AC ATP cAMP Enzyme-PO4 AC= Adenylyl cyclase Biological effect

19. The general Principles of chemical transmission: • Denervation supersensitivity: • If the nerve supplying the skeletal muscle is cut supersensitivity of the muscle to injected Ach occurs after denervation). • Mechanisms : • Receptor proliferation (up to 20 folds in sk. muscles). • Loss of transmitter removal mechanisms (e.g. reuptake and cholinesterase action on Ach).

20. * Supersensitivity can take place due to sustained pharmacological block of ganglionic transmission, blockade of post-synaptic receptors, resulting in rebound effects when the blocker drug is stopped. This is due to receptor upregulation e.g. rebound hypertension after sudden withdrawal of beta-blockers

21. Neuromodulation: Many neuropeptides affect membrane ion channels in such a way to increase or decrease excitability and thus control the firing pattern of the cell without participating directly as transmitters.

22. CATECHOLAMINE Synthesis & Storage Characteristics of a norepinephrine (NE)-containing catecholamine neuron. # Tyrosine (Tyr) accumulated by the neuron is metabolized to DOPA by tyrosine hydroxylase DOPA by DOPA decarboxylase metabolized to dopamine (DA). # The DA is taken up through the vesicular monoamine transporter into vesicles. # DA is metabolized to NE by dopamine-b-hydroxylase (DBH), which is found in the vesicle. Once NE is released, it can interact with postsynaptic noradrenergic receptors or presynaptic noradrenergic autoreceptors.

25. CATECHOLAMINE Synthesis & Storage

26. Uptake of catecholamines: transporter

28. ACETYLCHOLINESynthesis and Storage

29. Inactivation of Norepinephrine

30. The main effects of the autonomic NS: Organ Sympathetic Parasymp.

31. Heart b1-Agonist Ca ++ Vagus b1-receptor M Gs AC Gi kinase ATP cAMP Ca++ Heart rate Contraction Conduction

32. Organ Sympathetic Parasymp.

33. Organ Sympathetic Parasymp.

34. Organ Sympathetic Parasymp.

35. Organ Sympathetic Parasymp.

36. Classification of adrenoceptors • α-receptors: NE > Epi > isoprenaline • β-receptors: Isoprenaline > Epi < NE • α- antagonists • Ergot alkaloids • β1 : heart β2 : bronchi β3 : fat cells • α 1 :NE (Prazosin) • α 2 : methylnoradrenaline, clonidine (yohimbine) • Partial agonist:

38. Adrenoceptor agonists • Pharmcological actions: • Smooth muscle • All contracted by α1 (except GIT) IP3 (Ca)i ROCs BP Splanchnic vascular beds , veins, arteries Baroreceptors bradycardia Vas deferens, spleenic capsule, eyelid retractor muscles (nictitating membrane),

41. Predicting Responses