Cholinergic Receptors

Overview

• Importance: Crucial for the parasympathetic nervous system.
• Types: Two categories of cholinergic receptors: Nicotinic and Muscarinic.
• Definition: Respond to acetylcholine (ACh).

Nicotinic Receptors (N)

• Agonists: Acetylcholine and Nicotine.
• Types:
  1. Nicotinic Neuronal (N_N):
     • Locations: Autonomic ganglia and Central Nervous System (CNS).
     • Functions: Found in several CNS locations, involved in key nervous system functions.
  2. Nicotinic Muscle (N_M):
     • Locations: Neuromuscular junctions on skeletal muscles.
     • Function: Facilitate muscle contraction.

Mechanisms in Neurons

• Ion Channels: Ligand-gated (chemically gated) ion channels.
• Action: ACh binding opens sodium channels, leading to excitation (EPSP).
• Central Nervous System:
  • Functions: Memory, Arousal, Analgesia.
  • Importance: ACh and nicotinic receptors are integral to CNS circuitry.

Mechanisms in Skeletal Muscles

• Ion Flow: Sodium ions enter muscle cells, causing depolarization.
• Result: Triggers action potentials, muscle contraction.
• Process:
  1. ACh released from motor neuron.
  2. ACh binds to nicotinic receptors on muscle cells.
  3. Sodium influx depolarizes cell.
  4. Voltage-gated sodium channels trigger calcium release from sarcoplasmic reticulum.
  5. Calcium induces muscle contraction.

Muscarinic Receptors (M)

• Agonists: Acetylcholine and Muscarine.
• Types: M1, M2, M3, M4, M5.
• Focus: Main focus on M1, M2, M3.

Mechanisms

• Structure: G-protein coupled receptors (GPCRs), also known as serpentine receptors.
• Types of GPCRs:
  1. GQ Protein-Coupled (Stimulatory) Pathway: M1, M3, M5
     • Mechanism:
       • ACh binding activates GQ protein.
       • GQ activates phospholipase C.
       • Phospholipase C cleaves PIP2 into IP3 and DAG.
       • IP3: Releases calcium from intracellular stores.
       • DAG: Activates protein kinase C.
       • Result: Phosphorylation of proteins/enzymes, changing cell functions.
  2. G Inhibitory (Inhibitory) Pathway: M2, M4
     • Mechanism:
       • ACh binding activates G inhibitory protein.
       • Inhibits adenylate cyclase, reducing cAMP.
       • Inhibits PKA, preventing phosphorylation of proteins/enzymes.
       • Enhances potassium outflow, hyperpolarizing the cell.

Locations and Functions

• M1:
  • CNS: Cognitive functions (memory, arousal, cognition, analgesia).
  • Gastric Glands: Stimulates hydrochloric acid and pepsinogen secretion.
• M2:
  • Heart: Inhibits the SA node and AV node, reducing heart rate and force.
  • Pre-synaptic nerve terminals: Inhibits further ACh release.
• M3:
  • Exocrine glands: Lacrimal, salivary, sweat, pancreatic, and gastric glands stimulation.
  • Smooth muscle: Bronchoconstriction, GI tract motility, bladder contraction, defecation.
  • Eye: Ciliary muscle for near vision, constrictor pupillae for pupil constriction.
• M4, M5: Primarily in CNS, roles similar to other muscarinic receptors (cognition, memory, arousal).

Summary

• Nicotinic and Muscarinic receptors both respond to ACh but have different structures and functions.
• Nicotinic receptors are ion channels; Muscarinic receptors are GPCRs.
• Each type plays specific roles in different tissues and organs, influencing various physiological processes.