PMY 302: Autonomic Nervous System

• The autonomic nervous system (ANS) is the focus of the PMY 302 Introduction to Pharmacology course.
• Copyright 2023 Jeannie M Padowski, reproduction of the material is prohibited without consent.

Learning Objectives

• Describe the sympathetic and parasympathetic nervous systems regarding anatomy and neurotransmission.
• Contrast the effects of sympathetic and parasympathetic systems at the system and organ levels.
• Discuss the integration and regulation of autonomic nervous system effects.

Divisions of the Nervous System

• The central nervous system (CNS) includes the brain and spinal cord
• The peripheral nervous system (PNS) encompasses nerves connecting the rest of the body to the brain.
• The autonomic nervous system is involuntary.
• The somatic nervous system is voluntary.
• The sympathetic nervous system is responsible for fight or flight.
• The parasympathetic nervous system is responsible for rest and digest.

Functions of the Autonomic Nervous System

• The parasympathetic conserves energy, reduces heart rate, lowers blood pressure and respiration, increases secretions, and constricts pupils
• The sympathetic expends energy, increases heart rate, raises blood pressure and respiration, increases blood flow to skeletal muscles, and dilates pupils.

Autonomic Nervous System Pharmacology

• ANS pharmacology is intimidating due to its involvement with nearly all organ systems
• It is important to focus on key properties of each system impacted by ANS drugs.
• ANS drugs are vital in critical medical situations.
• Beta agonists treat asthma by opening airways.
• Cholinergic nerve gasses and antidotes
• Epinephrine treats anaphylaxis and shock.

Autonomic Nervous System Neuroanatomy & Neurotransmission

• The ANS automatically responds to environmental or bodily changes without conscious thought
• The ANS maintains blood pressure, manages continence, and adjusts vision according to conditions.
• ANS controls pupil constriction/dilation based on light detected by the retina.

Autonomic Nervous System Opposing Organ Effects

• Most organs receive innervation from both sympathetic and parasympathetic nerves, utilizing different neurotransmitters at different receptors.
• These opposing effects result from different chemicals and receptors
• An example is ACh constricting pupils, while NE dilates them.
  • A related type of antagonism? Physiological antagonism

Sympathetic vs. Parasympathetic

• The sympathetic and parasympathetic systems work in opposite ways.
• Both systems transmit signals from the CNS to organs in the periphery.
• They differ in function, structure, major neurotransmitters, and receptors.
• The sympathetic is catabolic and thoracolumbar, features long postganglionic fibers and is typically adrenergic.
• The parasympathetic is anabolic and craniosacral, features short postganglionic fibers and is generally cholinergic.

Autonomic Nervous System Anatomy

• The ANS employs a two-neuron signaling system for reaching target organs.
• A preganglionic neuron originates in the CNS and synapses with a postganglionic neuron.
• Postganglionic neuron cell bodies reside in autonomic ganglia and synapse onto target organs

Autonomic Nervous System Anatomy: Signaling System Types

• Parasympathetic uses long pre-ganglionic nerves with ganglia near the target organ and synapse 1:1
• Sympathetic uses short pre-ganglionic nerves with ganglia near the spinal cord that synapse onto many cells

Neurotransmitters

• Acetylcholine (ACh) is released by all pre-ganglionic neurons and all PSNS post-ganglionic neurons.
  • Acetylcholine synthesis occurs from acetyl coenzyme A (acetyl CoA) and choline.
  • ACh enzymatic degradation by acetylcholinesterase enzymes rapidly terminates ACh in the synapse.

Cholinergic Receptors

• Nicotinic ACh Receptors are ligand-gated ion channels found at the motor endplate/voluntary movement.
  • It is also found in all ANS ganglia and in the adrenal medulla.
• Muscarinic ACh Receptors.
  • GPCR receptors are found on target organs of post-ganglionic fibers, mainly in the PSNS.
  • Named after defining alkaloids: muscarine and nicotine

Catecholamines

• Catecholamines are monoamines that contain a catechol group.
  • includes dopamine, norepinephrine, and epinephrine.
  • all are products of tyrosine.

Norepinephrine

• Norepinephrine (NE) released in most post-ganglionic SNS neurons.
• Is produced via dopamine metabolism.
• NE is further metabolized into epinephrine (EPI).
• NE terminates mainly by reuptake transporters, and is sometimes inactivated by enzymes like MAO and COMT

Adrenergic Receptors

• There are two main types of adrenergic receptors.
• There are different subtypes that respond to catecholamines such as norepinephrine.
• Alpha 1 Receptors:
  • GPCR stimulatory, mostly on blood vessels
• Alpha 2 Receptors:
  • GPCR inhibitory, pre-synaptic a2 which decreases NE
• Beta 1 and 2 Receptors:
  • Both are GPCR stimulatory, which varies on location

GPCR Signaling Pathway

• Gs, Gi, and Gq signaling pathways should be familiar.
• These three mechanisms underlie the effect of autonomic drugs in every organ.
  • α₁, M₁,₃,₅ use Gq stimulatory to increase Ca++.
  • α₂, M₂,₄ use Gi inhibitory to decrease cAMP.
  • β₁ use Gs stimulatory to increase cAMP.
  • β₂ use Gs stimulatory to increase cAMP.
  • The adrenergic GPCR types can be remembered as “KISS” (q – i – s – s).

ANS Receptors Effect & Locations

• Receptor activation triggers the same GPCR cascade or ion flow no matter location, physiological impact depends on receptor expression.
• Knowing subtypes helps predict effects and side effects.
• Key information: Sites of receptor types, agonists, antagonists, and important effects.

Autonomic Nervous System Receptor Effects & Locations

Adrenergic receptors concentration often depends on place of neurotransmitter release by postganglionic neurons. Adrenergic neurotransmitters like EPI and NE circulate throughout the body from glands. Circulating NE and EPI act on adrenergic receptors like immune/blood cells.

Autonomic Nervous System Control of Organs

Dual Innervation and Dominant Tone

• Dual Innervation is most sites receive ANS input from SNS and PSNS. Exceptions: blood vessels, sweat glands (only SNS).
• Predominant tone is when in most organs, PSNS is the stronger influence on tissue function when the body is at rest (SNS exceptions mentioned prior)
  • When at rest, a muscarinic ACh receptor blocker has a greater impact than a NE.
  • The NE antagonist has larger effect under activated SNS during stress

Autonomic Nervous System Control of the Eye

• Pupil Diameter depends on the following activations:
  • SNS contracts dilator muscle, opening iris (mydriasis/dilation).
  • PSNS contracts circular muscle, constricting iris (miosis/pupil constriction).
• SNS activation produces aqueous humor, while a2 activation reduces production.
• PSNS activation contracts ciliary muscle, changing lens shape for near vision.

Autonomic Nervous System Control of Airways

• Bronchial diameteractions depend on the following activations:
  • PSNS contracts airway smooth muscle, causing bronchoconstriction via M3
  • SNS relaxes airway muscle, causing bronchodilation via B2
• The bronchial secretion actions depend on the following:
  • PSNS. Stimulation via M3 stimulate the goblet cells increase of mucus.
  • SNS has minor effect via B2 and increases clearance of secretions

Autonomic Nervous System GI tract

• Smooth Walls depend on what is stimulated.
  • PSNS the contracts to increase tone & movement via M3
  • SNS reduces tone and motility via α2, β2
• Sphincters (including esophageal and pyloric)
  • PSNS relaxes for transit via M3.
  • SNS constructs GI sphincters via a1
• Secretion Activation
  • SNS inhibits secretions via a2

Autonomic Nervous System Control the Bladder

• Urinary Bladder Walls actions depend on these:
  • PSNSM contracts detrusor muscle to expel urine via M3
  • SNS. activation relaxes detrusor via B3
• Urethral Sphincter actions the depend on:
  • PSNS relaxes the sphincter allow for urine passage via M3
  • SNS al activation constricts to hold urine
• SNS A activation contracts prostate smooth muscle, increasing urine flow.

Autonomic Nervous System Cardiovascular System

• The heart receives its input from PSNS and SNS
• Regulated attributes include:
  • Force
  • Heart rate
• Blood vessels directly controlled by SNS influence resistance/blood pressure.

Autonomic Nervous System Heart Rate

• An action on the pacemaker cells include:
• B contract the rate to generate action via nodes.
• M stimulation decreases the rate via nodes.

Autonomic Nervous System Control Force of Heart

• SNS. B1 activation increases contraction of cardiomyocytes via multiple Ca2+ handling actions.
• PSNS does not directly innervate cardiomyocytes.

Autonomic Nervous System vasculature

• SNS Beta-activation causes the relaxation (vasodilation) in the muscles located within the skeletal system via B2
• SNS activation smooth muscles contraction in the skin and blood vessels via A1 and A2
• PSNS stimulation direct innervation causes relaxing vasodilation

Autonomic Nervous System Blood Volume

• SNS activation causes the renal glands that ultimately increasing blood volume and drawing and retain water with in and though the body

Other Autonomic Nervous System receptor and actions

• B Activation

  • Relaxes Uterus

  • Ejaculation

    • immune response decrease

  • sweat glands M and a and B -In the liver activation results to glycogenolis and gluconeogenesis.

• alpha reduces Ne activation.

ANS Integration

• autonomic integration regulated from to the CNS and to the cells
• Regulation includes a negative feedback

CNS ANS Integration

• Integrate via spinal cord SNS/PSNS and endocrine to the sensory inputs

Homeostatic ANS Mechanisim

• Some ANS systems controlled for the hemostasis
• Drugs effect and alter certain thing that control pressure, however has other effect to try and counteract
• Autonomic is important for autonomic drugs

Presynaptic Autonomics

• Located along the spinal cord to try and allow the neuro transmission
• Feedback to allow modulated input

Explore the autonomic nervous system within the PMY 302 Introduction to Pharmacology course. Learn about the sympathetic and parasympathetic divisions, their functions, and how they regulate bodily processes. Understand the involuntary nature of the ANS and its contrast with the somatic nervous system.