Cell Signalling

• Forms of intercellular signalling


  • Contact-dependent
  • Paracrine
  • Synaptic
  • Endocrine

  
• Contact-dependent signalling


  Ligand is embedded in the plasma membrane of a cell and doesn't actually leave the cell. The ligand can bind to a receptor through cell to cell contact.
• Paracrine signalling


  Signalling cell secretes a molecule such as a hormone or another signalling molecule, which then targets cells that are very nearby — they act locally.
• Synaptic signalling


  Molecule is released at the synaptic cleft (it doesn't travel very far). The axon secretes a neurotransmitter when it receives an action potential, which then binds to receptors on the target cell.
• Endocrine signalling


  Signalling molecules are released into the bloodstream, the circulation can travel throughout the body and bind to receptor target cells that may be elsewhere in the body.
• Types of receptors


  • Cell surface receptors
  • Intracellular receptors

  
• Glucose regulation


  1. Insulin released from pancreas when glucose levels are high

  2. Glucagon released from pancreas when glucose levels are low
• Glycogen signalling pathway (liver)

  1. Glucagon binds to G-protein coupled receptor on liver cells

  2. G-protein binds GTP, dissociates and activates adenylyl cyclase

  3. Adenylyl cyclase converts ATP to cAMP

  4. cAMP binds and activates protein kinase A

  5. Protein kinase A activates phosphorylase kinase

  6. Phosphorylase kinase activates phosphorylase

  7. Phosphorylase breaks down glycogen to glucose-1-phosphate

  8. Glucose-1-phosphate dephosphorylated and released into blood

  
• Pharmacists should care about GPCR signalling as many drugs target GPCR pathways