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Autonomic Pharmacology--Introduction-Lecture I, slide 1

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Table of Contents
  • ANS Anatomy
    • Autonomic and Somatic Innervation
    • Autonomic Reflex Arc
    • Autonomic Reflex Arc: First Link
    • Sensory Fiber Neurotransmitter(s)
    • Autonomic Nervous System Neurotransmitters: Summary
    • CNS and the Autonomic Nervous System
      • Spinal Cord Reflexes
      • Hypothalamus and Nucleus tractus solitarii
      • Higher Centers
    • Peripheral ANS Divisions
  • Comparison between Sympathetic & Parasympathetic Systems
  • Sympathetic Nervous System Anatomy
    • Diagram Sympathetic System
    • Anatomical Outline
      • Paravertebral Ganglia
      • Prevertebral Ganglia
      • Terminal Ganglia
      • Adrenal Medulla
  • Parasympathetic System Anatomy
  • ANS Neurotransmitter Effector Organs
  • Eye
  • Heart
  • Arterioles
  • Systemic Veins
  • Lung

 
  • Skin
  • Adrenal Medulla
  • Skeletal Muscle
  • Liver
  • Posterior Pituitary

 
  • Interactions between Sympathetic & Parasympathetic Systems
  • "Fight or Flight": Characteristics of the ANS
  • ANS Neurotransmission
    • Neurotransmitter Criteria
    • Neurotransmission Steps:
      • Axonal Conduction
      • Storage and Release of Neurotransmitter
      • Combination of Neurotransmitter and Post-Junctional Receptors
      • Termination of Neurotransmitter Action
      • Other Non-electrogenic Functions
    • Cholinergic Neurotransmission
      • Transmitter Synthesis and Degradation
      • Acetylcholinesterase
      • Acetylcholine: Storage and Release
      • Site Differences:
        • Skeletal Muscle
        • Autonomic Effectors
        • Autonomic Ganglia
        • Blood vessels
      • Signal Transduction: Receptors
  • Adrenergic Transmitters: Biosynthetic Pathways
  • Adrenergic Neurotransmission: Introduction to the Neurotransmitters
  • Catecholamine Synthesis, Storage, Release and Reuptake
    • Enzymes
    • Catecholamine storage
    • Regulation of adrenal medullary catecholamine levels
    • Reuptake
    • Metabolic Transformation
    • Indirect-acting sympathomimetics
    • Release
  • Adrenergic Receptor Subtypes
    • ß-adrenergic receptors
    • Alpha-adrenergic receptors
    • Catecholamine Refractoriness
  • Other Autonomic Neurotransmitters
    • Co-transmission
      • ATP
      • VIP
      • Neuropeptide Y family
    • Purines
    • Nitric Oxide (Modulator)
  • Predominant Sympathetic/Parasympathetic Tone
  • Baroreceptor Reflexes
  • Pharmacological Modification of Autonomic Function
  • Autonomic Dysfunction

 

Autonomic Nervous System: Anatomical Considerations

Figure by Poul-Erik Paulev, M.D., D.Sci, Department of Medical Physiology 
University of Copenhagen, used with permission

Autonomic and Somatic Innervation
  • Skeletal muscle is innervated by somatic nerves, controlling voluntary actions
  • All other innervated structures are supplied by the autonomic or involuntary system.
  • Somatic system: No ganglia present
  • Autonomic nervous system (ANS) has ganglia.
    • these ganglia are sites at which preganglionic fibers form synaptic connections with postganglionic neurons
    • these ganglia are located outside the cerebrospinal axis
Other differences between Somatic and Autonomic Innervation
  • Motor nerves to skeletal muscle: myelinated
  • Postganglionic autonomic nerves are nonmyelinated
  • Denervation of skeletal muscle results in paralysis and atrophy
  • Denervated smooth muscle or glands retain some activity

 

 

Autonomic Reflex Arc
  • First link: Visceral autonomic afferents to the CNS
    • Non-myelinated, carried to the cerebrospinal axis by autonomic nerves (e.g.vagus and splanchnic)
    • Some autonomic afferents from skeletal muscle blood vessels and integumental structures may be carried in somatic nerves
    • Cell bodies of visceral afferents: (a) spinal nerves--in dorsal root ganglia; (b) cranial nerves-- in sensory ganglia
    • What information gets transmitted?
  • Mediated Information:
    •  visceral sensation (pain;referred pain)
    •  vasomotor reflexes
    •  respiratory reflexes
    •  viscerosomatic reflexes: Definition: Viscerosomatic: Pertaining to the viscera and body

Figure by Poul-Erik Paulev, M.D., D.Sci Department of Medical Physiology 
University of Copenhagen, used with permission

Substance P is an important sensory neurotransmitter, probably especially important in nociception, and is found in:

sensory afferent fibers dorsal root ganglia dorsal spinal cord horn

 

 

  • Other agents found in sensory neurons
    • somatostatin
    • vasoactive intestinal peptide (VIP)
    • cholecystokinin (CCK)
    • Calcitonin gene-related peptide (CGRP) (found with Substance P in cardiovascular sensory nerve fibers)

Dorsal Spinal Cord (substantia gelatinosa) Interneurons

  • Enkephalins: Antinociceptive due to inhibition of substance P release and reduced transmission to higher centers

 

CNS and the Autonomic Nervous System

Spinal Cord Reflexes
 sweating  blood pressure changes  temperature-induced changes in vasomotor tone  emptying of the bowels, bladder, seminal vesicles

 Hypothalamic and Nucleus tractus solitarii

Integration of ANS Functions
body temperature regulation water balance fat/carbohydrate metabolism blood pressure
emotions sexual response sleep respiration

 

Higher Centers

  • Posterior and Lateral Hypothalamic Nuclei are assocaited with integration of autonomic sympathetic input

  • Midline nuclei in the region of the Tuber cinereum and anterior nuclei Nuclei are assocaited with integration of autonomic parasympathetic input

 

Peripheral ANS: Divisions
Sympathetic: (Thoracolumbar outflow) Parasympathetic; (Craniosacral Outflow)

 

Autonomic Nervous System Neurotransmitters: Summary

Neurotransmitter: Acetylcholine

  • All Preganglionic Autonomic Fibers

  • Parasympathetic Fibers

  • A few post-ganglionic sympathetic Fibers

 

Neurotransmitter: Norepinephrine

  • Postganglionic Sympathetic Fibers

Neurotransmitter: Primary Afferents

  • Substance P and/or glutamate

 

Comparisons between Sympathetic and Parasympathetic Nerves

  • Sympathetic system has a broader distribution, innervating effectors throughout the body
  • Parasympathetic system is relatively limited

 

  • Sympathetic fibers show greater ramification.
  • Sympathetic preganglionic fibers may traverse through many ganglia before terminiating at its post-ganglionic cell.
    • Synaptic terminal arborization results in a single preganglionic fiber terminating on many post-ganglionic cells.
  • This anatomical characteristic is the basis for the diffuse nature of sympathic response in the human and other species.

 
  • The parasympathetic system has its terminal ganglia near the end-organ.
  • Sometimes there is but a one-to-one ratio relationship between pre-and post-ganglionic fibers. The ratio between preganglionic vagal fibers and ganglion cells may be much higher, e.g. 1:8000 for Auerbach's plexus.

 

Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotrasmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.107

 

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