Parasympathetic Nervous System

• Parasympathetic Nervous System

  Efferent fibers arise from the cranial and sacral regions of the CNS

  
• Cranial Nerves


  • oculomotor (III), facial (VII), glossopharyngeal (IX), and vagus (X) nerves

  
• Sacral Nerves

  • II, III, IV
• Muscarinic


  Classic agonist: Muscarine (Natural product found in some mushrooms)
• Muscarinic Receptor Subtypes


  • M1
  • M2
  • M3
  • M4
  • M5
• Nicotinic


  Classic agonist: Nicotine (Natural alkaloid most commonly found in tobacco)
• Nicotinic Receptor Subtypes


  • NN
  • NM
• Nicotinic - NN


  "N" stand for "neuron", Neuronal type, ganglion receptor, Found most commonly on postganglionic nerve cells
• Nicotinic - NM


  "M" is for muscle, Not part of the parasympathetic nervous system
• M1 Muscarinic Receptors


  • Gq/11 coupled receptors, IP3, DAG cascade, Has stimulatory effect

  
• M2 Muscarinic Receptors


  • Gi/o coupled receptors, Inhibition of cAMP, activation of K+ channels, Has inhibitory effects
• M3 Muscarinic Receptors


  • Gq/11 coupled receptors, IP3, DAG cascade, Has stimulatory effect

  
• M4 & M5 Muscarinic Receptors


  • Located in the CNS: Hippocampus, Substantia nigra, Less well characterized, May play a roll in certain neurological diseases

  
• Examples of Cholinoreceptors

  • NM
  • M1
  • NN
• In the parasympathetic nervous system, acetylcholine is the primary neurotransmitter in preganglionic and postganglionic cells
• Medications with anticholinergic side effects would not be expected to cause diarrhea, but does cause urinary retention, constipation, and blurred vision.
• The primary neurotransmitter used by neurons in the parasympathetic nervous system is acetylcholine
• Inhibition of acetylcholinesterase would prolong the half-life of acetylcholine in the synapse
• Cholinomimetic agents include muscarinic agonists such as pilocarpine, bethanechol, carbachol, and neostigmine.
• Parasympathomimetics are drugs that mimic or enhance the effects of acetylcholine on cholinergic receptors.
• The enzyme acetylcholinesterase breaks down acetylcholine to terminate its action in the synaptic cleft.
• The parasympathetic nervous system is involved in the regulation of heart rate, blood pressure, digestion, urination, defecation, salivary secretions, lacrimation (tear production), pupillary constriction, accommodation, and sexual function.
• Acetylcholine binds to muscarinic and nicotinic receptors to exert its effects in the parasympathetic nervous system.
• Antagonism at nicotinic receptors can occur through competitive or noncompetitive mechanisms.
• Carbamates (e.g., physostigmine) inhibit AChE activity irreversibly, while organophosphates (e.g., soman) do so reversibly.
• NM receptor is responsible for skeletal muscle contractions and function primarily within the central nervous system and at the neuromuscular junction.
• M2 receptors are a cholinoreceptor found primarily in the heart.