Lecture 3 - Receptor-effector systems

• Ligand-gated ion channels

  • Control the cell membrane potential
  • Response happens on a millisecond timescale
  • Examples include nicotinic acetylcholine receptor, GABA type A receptor, N-Methyl-D-aspartate (NMDA) receptor, 5-hydroxytryptamine type 3(5-HT3) receptor
• Drug-receptor combination for G protein-coupled receptors (GPCRs)

  • beta-adrenergic receptor (agonist: adrenaline, antagonist: propranolol)
  • histamine receptor (agonist: histamine, inverse agonist: antihistamines)
• Nuclear receptors


  • Control transcription of genes with hormone response elements
  • Require ligands to be able to cross the membrane
  • Account for 60% of prescribed drugs
• Response to ligand-gated ion channels


  Central aqueous channel opens in response to ligand or voltage, allowing passage of ions
• Receptor tyrosine kinases (RTKs)

  • Control cell growth, differentiation, and immune response
  • Activated by dimerisation followed by trans-autophosphorylation
  • Response happens on a timescale of hours
• G protein-coupled receptors (GPCRs)


  • Respond to light, sound, smell, taste, hormones, neurotransmitters
  • Target of approximately 40% of all developed drugs
  • Induce conformational changes in associated trimeric G proteins to activate them
• 4 main subtypes of receptor-effector systems

  • G protein-coupled receptors (GPCRs)
  • Ligand-gated ion channels
  • Receptor kinases (RTKs)
  • Nuclear receptors
• Drug-receptor combination for ligand-gated ion channels

  • Consist of individual subunits with 4 transmembrane helices
  • The more ligand molecules that are bound, the more 'open' the receptor
  • Drugs may bind at multiple different sites and exert similar or dissimilar effects
• Receptor tyrosine kinases

  RTKs
• GPCRs

  • beta-adrenergic receptor (agonist: adrenaline, antagonist: propranolol), histamine receptor (agonist: histamine, inverse agonist: antihistamines)
• GPCRs

  G protein-coupled receptors
• Receptor tyrosine kinases

  • epidermal growth factor receptor (agonist: EGF, antagonist: afatinib), platelet-derived growth factor receptor (agonist: PDGF, antagonist: crenolanib)