1. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. LECTURE 10 Sympathatic nervous system

2. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Anatomy of the sympathetic nervous system  The origin is from thoracolumbar segments “all thoracic + lumbers L1, L2, L3 and L4 ”  They have short preganglionic fibers, and it relays in sympathetic chain ganglia & release Ach in these ganglia  They have long postganglionic fibers that innervate their body organs & release Norepinephrine as a neurotransmitter there

3. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Neurotransmission at adrenergic neurons  Synthesis of norepinephrine (NE)  Storage of dopamine (DA) and NE in vesicles  Release of NE  Metabolism (COMT 20% + MAO 80%)  Binding to receptors  Uptake mechanism

4. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

6. Deactivation of NE  re-uptake by presynaptic nerve terminal  metabolize by COMT (catechol-o-methyl transferase).  Metabolize by MAO (monoamine oxidase).

7. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenoceptors  The adrenergic receptors are classified into  α1  α2  β1  β2  Β3  There are some subtypes

8. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Receptors α Subtypeβ Subtype ↑ Phospholipase C↓ Adenylate cyclase α1α1α2α2 β1, β2 & β3 ↑ Adenylate cyclase smooth muscles - Presynaptic adrenergic nerve terminal -CNS -β cells of pancreas β1 (heart) β2 (smooth muscles) β 3 (lipocytes) Adrenergic Receptors β Subtype Adrenergic Receptors α Subtype Adrenergic Receptors

9. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. α1-adrenergic Receptors  In all sympathetic target organs except heart  Response  Constriction of blood vessels  Dilation of pupils  Contraction of sphincters

10. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. α 1 – adrenoceptors (continue) Site of α 1 – adrenoceptors & the effects of their stimulation α 1 – adrenoceptors (continue) Site of α 1 – adrenoceptors & the effects of their stimulation  In vascular smooth muscle.  α 1 stimulation cause vasoconstriction (VC) : Vasoconstriction in the skin & viscera cause increase total vascular resistance (TVR) causing increase blood pressure (BP) Vasoconstriction in the skin & viscera cause increase total vascular resistance (TVR) causing increase blood pressure (BP)  α1 – adrenoceptors the most determine of arteriolar tone. When their stimulated no others receptors have an affects on BP. So, hypertension may be treated by blocking α1 Vasoconstriction in the nasal blood vessels cause relief of congestion Vasoconstriction in the nasal blood vessels cause relief of congestion  In the radial muscle of iris.  α1 stimulation causes contraction of the radial muscle causing mydriasis (dilation of the pupil)

11. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Continue….  In the smooth muscle of the sphincters of GIT.  α1 stimulation cause contraction of all sphincters  In the smooth muscle of internal sphincter of urinary bladder (Very important). α 1a subtypes stimulation cause contraction and closure of the sphincters (precipitate urinary retention)  In the seminal vesicles. α stimulation cause ejaculation. Thus, all α blockers inhibit ejaculation  In the liver.  α1 stimulation causes increase glycogenolysis & gluconeogenesis

12. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. α2-adrenergic Receptors  At presynaptic adrenergic neuron terminals  Activation inhibits release of norepinephrine  Insulin secreting β cells of pancrease

13. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. α 2 –adrenoceptors Site of α 2 – adrenoceptors & the effects of their stimulation  In adrenergic nerve terminals (presynaptic).  α 2 stimulation cause decreased Norepinephrine release (autoregulatory mechanism). It opposes the action of sympathetic stimulation.  In pancreas.  causes decreased insulin release   In platelets.  Increase platelets aggregation via c-AMP

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15. β1-adrenergic Receptors  In heart and kidneys  Response  Activation increases heart rate and force of contraction of heart.  Increases release of renin

16. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. β 1 – adrenoceptors  In the heart. β 1 stimulation causes  In S.A node : increase heart rate (HR) (+ve chronotropic)  In Myocardium tissue : increase contractility (+ve inotropic)  In Conducting system : increase conduction velocity (+ve dromotropic)  Increase ectopic beats  In the Juxtaglomerular Apparatus of the kidney. β 1 stimulation cause increased renin release. Then causes increase in BP

17. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. β2-adrenergic Receptors  In all sympathetic target organs except the heart  Inhibit smooth muscle  Control metabolism in the liver

18. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. β 2 – adrenoceptors  In the bronchial smooth muscle β 2 stimulation causes relaxation of smooth muscle (bronchodilatation)  In the smooth muscle of blood vessels supplying the skeletal muscle. β 2 stimulation causes relaxation of smooth muscle  Vasodilatation(VD)  This VD effects is usually masked by the potent VC effect of α1 – receptors

19. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Continue  In the smooth muscle of GIT wall.  β 2 stimulation cause relaxation of the wall leading to decreased peristalsis  In the smooth muscle of the wall of urinary bladder.  β 2 stimulation causes relaxation of the wall  Note: Adrenergic stimulation is opposite to the cholinergic in the wall and sphincters in GIT and genitourinary tract.

20. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Continue  In the smooth muscle of the uterus  β 2 stimulation causes relaxation of the uterus (Ritodrine delay the labor)  In the liver.  β 2 stimulation causes increased Glycogenolysis & Gluconeogenesis  Effect on potassium.  β 2 stimulation increase potassium influx.

21. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. β3 receptors  In adiopse tissue  Stimulates lipolysis

22. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. D1 receptor  D1(occurs in renal vascular bed)  Vasodilatation of renal arterioles.

23. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Molecular mechanism of adrenergic receptors  All are G-protein linked receptors that act via IP3 or cAMP  Example β2 receptor id Gs receptor increases cAMP and subsequent events intracellular leads to cellular changes and response; relaxation of smooth muscles, or stimulation of metabolism.

24. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Smooth muscle dilation via β2 receptors

25. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Receptor types (G-protein linked receptors)

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28. OrganSympatheticRParasympatheticR HeartStimulantβ1β1Depressant of atriaM2 Smooth Muscles a- BVConstriction Dilation (BV Sk. M.) Kidney Vasculature αβ2Dαβ2D No innervation (dilation by EDRF) M3 b- BronchiNo innervationβ2β2Constriction ↑ Secretion M3 c- GIT Smooth muscle Sphincter Glands ↓ motility Constriction ----- β2α1β2α1 ↑ motility Dilation ↑ Secretion ↑Gastric acid Enteric system M3 M1 d- Urinary Bladder Smooth muscle Sphincter Relaxation Constriction β2α1β2α1 Contraction Dilation M3

29. Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. OrganSympatheticRParasympatheticR e- Eye: * Iris -Radial muscle -Circular muscle *Ciliary Muscle Contraction Relaxation (slight) α1β2α1β2 Constriction Contraction M3 Glands: Salivary Glands Lacrimal Glands Sweat Glands: Thermoregulatory Apocrine (stress) ↑ Secretion No effect ↑ Secretion α1, β2 -------- M3 α1 ↑ Secretion M3 Metabolic Functions: Liver Adipose tissue Kidney Gluconeogenesis Glycogenolysis Lipolysis Renin release β2β2β3β1β2β2β3β1