Session 4 - G protein coupled receptor signalling

• Basic structure of GPCRs?

  • single polypeptide chain
  • 7 transmembrane - spanning regions
  • Extracellular N-terminal
  • Intracellular C-terminal
• sympathetic activity increases slope of the pacemaker potential.
• parasympathetic activity decreases slope of the pacemaker potential.
• sympathetic effect mediated by beta 1 receptors G-protein coupled receptors (Gs)
• parasympathetic effect mediated by M2 receptors G-protein coupled receptors (Gi).
• Sympathetically released noradrenaline or pharmacological doses of adrenaline act on α1 adrenoceptors in vascular smooth muscle to cause vasoconstriction.
• Parasympathetically released acetylcholine can interact with bronchiolar smooth muscle M3 muscarinic receptors to cause bronchoconstriction
• Small GTPases - monomeric G proteins
• GTPase activating proteins (GAPs – ‘off’ switch)
• • GDP exchange factors (GEFs - removal of GDP and binding of GTP ’on ’switch)
• Cholera mechanism?

  • CTx ribosylates Gsα-prevents deactivation.
  • Cellular cAMP increases
  • ‘over activation’ of PKA
  • PKA phosphorylates CFTR Cl-channel
  • Rapid efflux of Cl
  • diarrhoea
• pertussis toxin (Whooping Cough) ribosylates (Giα)
• Analgesics and opioid receptors

  Bind to receptors in regions of the CNS involved in transmission and modulation of pain.

  Dampen nerve signals transmitting pain.
• Overdose of opioids?

  Affects neural pathways controlling respiration causes respiratory depression

  requires naloxone an opioid antagonist.
• Drugs and therapeutic effects?

  -

  A) beta 2 adrenoreceptor

  B) agonist

  C) beta 1 adrenoreceptor

  D) antagonist

  E) H1 and H2 receptors

  F) Anatgonist

  G) Opioid receptors

  H) anatgonist