Receptor Signalling

Anmerkungen:

• Depending on the type of receptors. The rate of which agent binds to receptors and the effect may take milliseconds to hours/days. In general, the surface receptors takes miliseconds to act while the nuclear receptors takes hours or days, conversely, the surface receptors are fast acting and also fast dissipating, while the nuclear ones last longer before the agent break down.

1. G-Proteins

   Anmerkungen:

   • Also known as the 7TM receptor, one example is rhodopsin receptor where the receptor creates secondary messengers to do other stuff. There are a few kinds of G-proteins.
   1. Protein Types

      Anmerkungen:

      • G-protein comes in 3 units at below membrane level, the alpha ,beta and gamma units. The beta and gamma ones are always together and will dissociate together, the effects of the alpha G-protein will determine what effects it will have on the receptors.
      1. G-protein alpha i

         Anmerkungen:

         • I = inhibitory Same thing, the ligand bind to the receptor and it causes a conformational change at the tail, whereby the GTP will bind and fall off the 3 sets of g-protein, the G protein will then dissociate and the Gpai will bind to the adenylate cyclase to arrest the change of ATP to cAMP.
      2. G-protein alpha s

         Anmerkungen:

         • An easier way to remember is that S= stimulates. The ligand bind to the binding site and causes conformational changes to the protein. GTP comes on and off the G protein sets and the Gpas dissociates and bind with adenylate cyclase and the enzymes uses ATP to turn into cAMP.
      3. G-protein alpha q

         Anmerkungen:

         • q alpha proteins does things differently, it changes the porosity of the endoplasmic reticulum by binding it with phospholipase beta and it in turn cleaves the PIP2 into Ip3.
   2. Secondary Messengers

      Anmerkungen:

      • Usually the effects of the G-protein are to release secondary messengers The messenger types: Cyclic nucleotides: such as cAMP or cGMP. Phospholipids: PIP3 IP3 and DAG Ions: Glycerol Gases: nitric oxide
      1. Calcium

         Anmerkungen:

         • 1st experiment shows the ringer solution by which calcium stimulates the heart. Calcium causes, contraction of muscle, release of neurotransmitter, cell proliferation and migration, secretion of hormones, Regulates gene expression. Extracellular calcium concentration is 10000x greater than intracellular calcium concentration. It is stored in the endoplasmic reticulum or the sarcoplasmic reticulum. It then release to cytoplasm upon signalling to the alpha-q protein.
   3. Kinase cascade

      Anmerkungen:

      • The cascade is by which one receptor causes multiple actions by activating secondary receptors more and more. One obvious example is the cAMP cascade to glucose.
2. Kinase linked Receptor Signalling

   Anmerkungen:

   • The hormone react witht he receptor and dimerised and it leads to autophosphorylation and it leads to a kinase cascade.. E.g THE MAPK signalling pathway. It sends phosphorylation all the way into the nucleus.
3. Activating/Deactivating Receptors

   Anmerkungen:

   • Inverse agonist turns off the receptors
4. Desensitisation

   Anmerkungen:

   • Refer to 2 lectures ago. where the desensitisation process takes place. In detail, the receptors are being recycled or break down. If the arrestin binds to the kinase and stops the G-protein. It thens gets recycled, if not it will be sent to be degraded when it wore out.

   Anlagen:

   • Site of Drug Action: Dose Responses