Autonomic Nervous System Overview

Nomenclature

• The Parasympathetic Nervous System (PSNS) is also called:
  • Cholinergic
  • Muscarinic
• The Sympathetic Nervous System (SNS) is also called:
  • Adrenergic

Anatomy

• PSNS Nerves (Craniosacral):
  • Originate from the top and bottom of the spinal cord
• SNS Nerves (Thoracolumbar):
  • Originate from the middle of the spinal cord

ANS Anatomy

• The SNS and PSNS both have ganglia
• The neurotransmitter released at the ganglia is acetylcholine (ACh)
• The receptors in the ganglia are nicotinic receptors

Neurotransmitters (NT)

• Acetylcholine is synthesized from Acetyl CoA and Choline
• Acetylcholine is stored in synaptic vesicles

ANS Anatomy - The Adrenal Medulla:

• The adrenal medulla is source of NT, releasing 80% epinephrine (Epi) and 20% norepinephrine (NE)

Neurotransmitters (NT): Synthesis

• Key NT like dopamine, norepinephrine, and epinephrine are synthesized from tyrosine
• The catecholamines (dopamine, norepinephrine, epinephrine) are a type of NT synthesized from tyrosine

Receptor Distribution: Cholinergic

• There are two types of cholinergic receptors: Nicotinic and Muscarinic
• Nicotinic receptors are found in:
  • Muscle
  • Ganglia
  • Adrenal Medulla
  • Central Nervous System (CNS)
  • Immune System
• Muscarinic receptors are divided into 5 subtypes:
  • M1, M3, M5: G-protein coupled (Gq)
  • M2, M4: G-protein coupled (Gi)

PSNS-Receptors

• PSNS Receptors are referred to as Muscarinic (M)
• Most drugs targeting M receptors are not classified by subtype
• Fewer drugs target M receptors than adrenergic receptors
• M receptors play an important role in drug side effects

M1, M3, M5 Receptors

• G-protein coupled (Gq)
• Found in:
  • Smooth Muscle:
    • Contraction
  • Bladder:
    • Contraction

M2, M4 Receptors

• G-protein coupled (Gi)
• Found in:
  • Heart:
    • Decreased rate, contraction
    • Decreased heart rate

PSNS-Receptors

• The effects of muscarinic agonists oppose the effects of adrenergic agonists
• Effects of muscarinic agonists:
  • Heart:
    • Decreased rate
    • Decreased contraction
  • Lungs:
    • Bronchoconstriction
  • Sphincters (GI and bladder):
    • Relaxation
  • Walls:
    • Contraction of bladder and GI tract walls

To Pee or Not to Pee - Bladder and Urination

• PSNS response in the bladder:
  • M3 in bladder wall: contracts
  • M3 in sphincter: relaxes
  • This results in urination

PSNS-Receptors

• Increased secretion:
  • Salivary
  • Respiratory
  • Tears
• Eye: (more on this later)

PSNS-Receptors

• M receptors play an important role in CNS
• M Receptors are important for cognitive function

Ligands for Muscarinic Receptors

• Direct stimulation:
  • Use of an agonist
• Indirect stimulation:
  • Acetylcholinesterase inhibitors increase the concentration of acetylcholine

Indirect-Acting Cholinergic Drugs

• Cholinesterase can bind to 3 types:
  • Acetylation:
    • Rapid Recovery
    • Physiological
  • Carbamylation:
    • Slower Recovery
    • Reversible drugs (e.g., neostigmine)
  • Phosphorylation:
    • No recovery
    • Irreversible drugs (e.g., "nerve gases")

Indirect-Acting Cholinergic Drugs:

• Irreversible cholinesterase inhibitors have been used in chemical warfare

Excess Cholinergic Response

• Excessive cholinergic response can cause:
  • Excessive secretion
  • Other related side-effects

Alpha-1 Adrenergic Receptors

• G-protein coupled (Gq)
• Causes contraction

Sympathetic Nervous System (SNS)

• Alpha-2 (α-2)
  • Function: inhibits the release of norepinephrine

Alpha-2 Agonists

• Binding of alpha-2 receptor agonist:
  • Inhibits the release of norepinephrine

Sympathetic Nervous System (SNS)

• Beta-1 (β-1)
  • Function: stimulates the heart
  • Location:
    • Heart:
      • Increased heart rate
      • Increased atrioventricular conduction
      • Increased contractility

Beta-1 Adrenergic Receptors

• G-protein coupled (Gs)
• Found in:
  • Heart:
    • Increased heart rate
    • Increased contractility

Beta-1 Adrenergic Receptors

• Liver, kidney, and uterus are innervated by the SNS
• Kidney:
  • Beta-1 receptors stimulate renin release
  • Renin causes increased blood pressure

Beta-2 Adrenergic Receptors

• Function: relaxation of smooth muscle
• Location:
  • Lungs: Bronchodilation
  • Blood vessels in skeletal muscle: Vasodilation
  • GI tract, bladder, uterus: relaxation of walls

Beta-2 Adrenergic Receptors

• G-protein coupled (Gs)
• Found in:
  • Lungs: Bronchodilation

To Pee or Not to Pee - Bladder & Urination

• SNS response in the bladder:
  • β-2 in bladder wall: relaxes
  • α-1 in sphincter: contracts
  • This results in not urinating

Beta-2 Adrenergic Receptors

• Liver, kidney, and uterus innervated by the SNS
• Liver:
  • Beta-2 receptors mediate glucose release by:
    • Gluconeogenesis: formation of new glucose
    • Glycogenolysis: breakdown of glycogen to glucose

Ligands for Adrenergic Receptors

• Sympathomimetics mimic stimulation of the SNS:
  • Direct activation of adrenergic receptors
  • Increased NT in the synapse

Sympathomimetics

• Increasing NT in the synapse by:
  • Increasing neurotransmitter release
  • Inhibiting reuptake of neurotransmitter

Fate of Neurotransmitters

• Reuptake pumps sit presynaptically, remove neurotransmitters from the synapse

Sympathomimetics

• Inhibiting neurotransmitter reuptake increases the amount of NT in the synapse

Sympathomimetics

• Increasing NT in the synapse:
  • Inhibiting neurotransmitter reuptake is more effective
  • Muscarinic antagonists can also be used
  • Beta-2 agonists can also be used, but have minimal effect

Case #2

• A compound causes the following:
  • Skeletal muscle vessels to relax
  • Uterus relaxation
  • Bronchodilation
• This compound is likely a beta-2 agonist

ANS effects in the circulation (Summary/Review)

• SNS:
  • β-2 receptors (skeletal muscle): Vasodilation
  • α-1 receptors: Vasoconstriction
• PSNS:
  • Minimal contribution to circulation
  • Stimulation of M3 causes nitric oxide release, leading to vasodilation

Case #2

• A compound causes the following:
  • Skeletal muscle vessels to relax
  • Bladder wall relaxation
  • Bronchodilation
• This compound is likely a beta-2 agonist

ANS Effects in the Bladder (Summary/Review)

• SNS:
  • β-2 receptors (bladder wall): Relaxation
  • a-1 receptors (sphincter): Contraction
  • Result: Do not pee
• PSNS:
  • M3 in bladder wall: Contraction
  • M3 in sphincter: Relaxation
  • Result: Pee

Test your knowledge on the anatomy and functions of the Autonomic Nervous System, including the Parasympathetic and Sympathetic Nervous Systems. This quiz covers nomenclature, neurotransmitter synthesis, and the roles of various receptors and ganglia. Challenge yourself to see how well you understand these complex systems.