Autonomic Nervous System: PSNS and SNS: lecture 7

• The autonomic nervous system (ANS) divides into the parasympathetic (PSNS) and sympathetic (SNS) nervous systems.
  • The PSNS is responsible for "rest and digest" functions.
  • The SNS mediates "fight or flight" responses.
• Most organs receive input from both the PSNS and SNS.
  • The PSNS and SNS generally mediate opposing responses in effector organs, acting as physiological antagonists.
  • Exceptions include the adrenal, lacrimal, and sweat glands, pilomotor muscles, and blood vessel smooth muscle.

Anatomy of PSNS and SNS

• The PSNS originates in the cranial and sacral spinal cord.
• The SNS originates in the thoracic and lumbar spinal cord.
• Both systems consist of two-neuron systems, with pre- and postganglionic fibers.
• Ganglia are aggregations of cell bodies of postganglionic neurons.

SNS Anatomy and Function

• SNS ganglia are located near the spinal cord, featuring short preganglionic and long postganglionic fibers.
• One preganglionic neuron synapses with many postganglionic fibers.
• This arrangement leads to rapid sympathetic responses.

PSNS Anatomy and Function

• PSNS ganglia are close to or within target tissues, featuring long preganglionic and short postganglionic fibers.
• One preganglionic neuron synapses with one postganglionic fiber.

Communication in the ANS

• Autonomic nerves are classified based on the neurotransmitter they release.
• Acetylcholine (ACh) was the first neurotransmitter identified and regulates both branches of the ANS.
  • Cholinergic neurons release ACh.
• Norepinephrine (NE) is released in tissues receiving sympathetic innervation most of the time.
  • Most postganglionic SNS neurons release NE.
• The adrenal gland secretes epinephrine (EP).
  • EP is also known as adrenaline, and neurons that release NE/EP are referred to as adrenergic.

Autonomic Receptors: Cholinergic

Muscarinic Receptors

• Muscarinic receptors (M1, M2, M3, M4, M5) are found in organs innervated by the PSNS, with M2 and M3 being prominent.
  • M2 receptors are found in the heart.
  • M3 and M5 receptors are found on endothelial cells.
    • These can be activated by drugs.
  • M3 receptors are found in sweat glands innervated by cholinergic SNS fibers.
  • All subtypes are found in the CNS.

Nicotinic Receptors

• Nicotinic receptors are of two types:
  • Nn (neuronal) are found in all ganglia of the PSNS and SNS.
  • Nm (muscle) are found on skeletal muscles.

Autonomic Receptors: Adrenergic

• Adrenergic receptors are found in organs innervated by the SNS and CSNS.
  • Their location and subtype determine the tissue response.

Alpha-Adrenergic Receptors

• Alpha receptors include α1 and α2 subtypes.
  • α1 receptors cause constriction in blood vessels and smooth muscle contractions.
  • α1 receptors are activated by NE and EP.

Beta-Adrenergic Receptors

• Beta receptors include β1, β2, and β3 subtypes.
  • β1 receptors are activated by NE/EP in the heart.
  • β2 receptors are selectively activated by EP, requiring high levels.
  • Activation of β2: EP >>> NE

Tonic Activity in the ANS

• Most tissues receive input from both the PSNS and SNS, acting as physiological antagonists.
• Autonomic drugs, stress, and environmental input can alter the balance of neurotransmission.

Cholinergic Transmission

• ACh is synthesized by the enzyme choline acetyltransferase (ChAT).
• ACh is degraded by the enzyme acetylcholinesterase (AChE).
• ACh activates muscarinic and nicotinic receptors.
  • Muscarinic receptors (M1, M2, M3, M4, M5) are G protein-coupled receptors.
    • Activation increases IP3 and DAG (stimulatory) and decreases cAMP (inhibitory).
  • Nicotinic receptors (Nn, Nm) are ion channels and are stimulatory.

Cholinergic Effects in Blood Vessels

• Although there is no PSNS input to blood vessels, cholinergic receptors are present on endothelial cells.
  • Direct agonists can relax vascular smooth muscle.

Adrenergic Transmission

• Synthesis involves three steps:
  • Tyrosine hydroxylase.
  • Dopa decarboxylase.
  • Dopamine β-hydroxylase.
• Termination occurs via:
  • Re-uptake.
  • Diffusion away from the synapse.
• Metabolism occurs via Monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT).

Adrenergic Transmission Details

• Dopamine is transported into synaptic vesicles and converted to NE by β-hydroxylase.
• Epinephrine secreted by the adrenal medulla circulates via the blood to various tissues.
• Adrenoceptors are linked to G-protein second messenger systems.

Adrenoceptor Actions

• α1 receptors function similarly to M1, M3, and M5 receptors, causing constriction and activation.
• α2 receptors function similarly to M2 and M4 receptors, promoting relaxation.
• β1, β2, and β3 receptors increase cAMP.
  • β1 receptors in the heart increase the rate and force of contraction.
  • β2 receptors in smooth muscle cells cause relaxation.
    • These are found in blood vessels (supplying skeletal muscle), the bronchial tree, uterine walls, GI tract, and bladder walls.
  • β3 receptors in fat cells increase lipolysis.

Effects of Direct-Acting Receptor Agonists

Cardiovascular System

• Heart:
  • M2 decreases heart rate.
  • β1 increases heart rate.
• Blood vessels (most):
  • M3 causes vasodilation (relaxation).
  • α1 causes vasoconstriction (activation).
• Blood vessels (skeletal muscle):
  • β2 causes vasodilation (relaxation).
  • Only NE is released, no adrenal release.

Other Effects

• M3 causes contraction, increasing activity and secretion (activation).
• β2 causes relaxation of smooth muscle.
• α1 causes constriction of sphincters (activation).

Autonomic Drugs

• Autonomic transmission can be inhibited or stimulated by chemicals affecting neurotransmitter:
  • Synthesis
  • Storage
  • Release
  • Receptor activation
  • Re-uptake or inactivation

The autonomic nervous system divides into the parasympathetic (PSNS) and sympathetic (SNS) nervous systems. Most organs receive input from both the PSNS and SNS, generally mediating opposing responses. Both systems consist of two-neuron systems, with pre- and postganglionic fibers.