Muscarinic Receptors Overview

Muscarinic Receptors

Overview

• Muscarinic receptors are a type of acetylcholine receptor
• Found in the peripheral nervous system (PNS) and central nervous system (CNS)
• Mediate the effects of acetylcholine, a neurotransmitter

Subtypes

• Five subtypes: M1, M2, M3, M4, and M5
• Each subtype has distinct pharmacological and functional properties
• M1, M3, and M5 are Gq-coupled, leading to increases in inositol trisphosphate and calcium
• M2 and M4 are Gi-coupled, leading to decreases in cAMP

Functions

• Regulate various physiological processes, including:
  • Heart rate and contractility
  • Smooth muscle contraction and relaxation
  • Exocrine gland secretion
  • Cognitive function and memory
  • Neurotransmitter release

Agonists and Antagonists

• Agonists: stimulate muscarinic receptors, mimicking the effects of acetylcholine
  • Examples: muscarine, pilocarpine, andbethanechol
• Antagonists: block the action of acetylcholine on muscarinic receptors
  • Examples: atropine, scopolamine, and tolterodine

Clinical Significance

• Muscarinic receptors are involved in various diseases and disorders, including:
  • Alzheimer's disease
  • Parkinson's disease
  • Myasthenia gravis
  • Overactive bladder
  • Glaucoma
• Targeted by medications for treatment of these conditions

Muscarinic Receptors

Overview

• Muscarinic receptors are a type of acetylcholine receptor found in both the peripheral nervous system (PNS) and central nervous system (CNS).
• They mediate the effects of acetylcholine, a neurotransmitter.

Subtypes

• There are five subtypes of muscarinic receptors: M1, M2, M3, M4, and M5.
• Each subtype has distinct pharmacological and functional properties.
• M1, M3, and M5 subtypes are Gq-coupled, leading to increases in inositol trisphosphate and calcium.
• M2 and M4 subtypes are Gi-coupled, leading to decreases in cAMP.

Functions

• Muscarinic receptors regulate various physiological processes, including:
  • Heart rate and contractility
  • Smooth muscle contraction and relaxation
  • Exocrine gland secretion
  • Cognitive function and memory
  • Neurotransmitter release

Agonists and Antagonists

• Agonists stimulate muscarinic receptors, mimicking the effects of acetylcholine.
  • Examples of agonists include muscarine, pilocarpine, and bethanechol.
• Antagonists block the action of acetylcholine on muscarinic receptors.
  • Examples of antagonists include atropine, scopolamine, and tolterodine.

Clinical Significance

• Muscarinic receptors are involved in various diseases and disorders, including:
  • Alzheimer's disease
  • Parkinson's disease
  • Myasthenia gravis
  • Overactive bladder
  • Glaucoma
• Muscarinic receptors are targeted by medications for the treatment of these conditions.

Muscarinic Receptors

Phospholipase C Activation

• Phospholipase C (PLC) is activated through the Gq protein pathway when muscarinic receptors bind to agonists
• PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)
• IP3 binds to IP3 receptors on the endoplasmic reticulum, releasing calcium ions from the ER into the cytosol
• DAG activates protein kinase C (PKC), which phosphorylates and activates various downstream targets

Gq Protein Pathway

• Muscarinic receptors are coupled to Gq proteins, which are heterotrimeric G proteins composed of α, β, and γ subunits
• Activated Gq proteins release the βγ subunits, which interact with PLC to activate it
• Gq proteins are responsible for activating PLC when muscarinic receptors are stimulated

cAMP Response Element

• Muscarinic receptors can also inhibit the production of cyclic adenosine monophosphate (cAMP) through the Gi protein pathway
• cAMP is a second messenger that activates protein kinase A (PKA), which phosphorylates and activates the cAMP response element-binding protein (CREB)
• CREB is a transcription factor that regulates gene expression in response to changes in cAMP levels
• Muscarinic receptor-mediated inhibition of cAMP production leads to decreased CREB activity and altered gene expression