PD – Receptor activity

Master answer

Second Messenger

• A downstream intracellular signalling molecule that is either released or inhibited by drug binding to its receptor.
• Examples include cAMP and cGMP.

Steps in activation of second messenger

1. Ligand binding to extracellular site
2. Conformation change in receptor
3. Activation of intracellular domain of receptor
4. Activation of enzymatic process at intracellular site effector site
5. Change in second messenger concentration
6. Action of second messenger on substrate
7. Response

Examples:

• cAMP
  • NA, ACh (M2), ACTH, ANP, Glucagon, PTH, TSH.
  • Primary effector adenylyl cyclase.
  • Secondary messenger cAMP.
  • Secondary effector PKA
• cGMP
  • ANP and NO.
  • Primary effector guanylyl cyclase.
  • Secondary messenger cGMP.
  • Secondary effector Protein kinase G (cGMP-dependent protein kinase)
• Phosphoinositol signalling
  • Noradrenaline, ACh (M1/M3). Signal transducer Gq,
  • Primary effector PLC,
  • Secondary messenger IP3/DAG,
  • secondary effector PKC
• Arachidonic acid pathway
  • Histamine.
  • Primary effector phospholipase A.
  • Second messenger arachidonic acid.
  • Secondary effector COX/lipoxygenase.
• Tyrosine kinase pathway
  • Insulin, IGF, PDGF.
  • Primary effector Ras.
  • Second messenger Ras-GTP.
  • Secondary effector MAP3K (raf)

Gladwin 2016

Answer by Gladwin