Drug Targets, Receptors

Nota:

• Receptors are a means to communication. Cell to cell communication relies on the receptors and the signalling agents. One such example is the receptors on leukocytes as it changes cells and mediatory agents to flow to the centre of wound

1. Lock and Key model

   Nota:

   • Receptive substances bind to certain stuff. As in "Agents cannot act without binding" 2 types of agents: Endogenous agonist: Specific binding agent and a lock, more of which the agent is manufactured by the same body. Exogenous agonist: Analogous to the bobby pin, a artificial "key" not manufactured by the same body. Antagonist does not have an effect by itself, but it is like a blockage to a key.
2. Senses

   Nota:

   • Eyes: Rhodopsin Receptors in the eyes (G-protein coupled receptors) Mouth: G-protein coupled taste receptors. Smell: G-protein coupled Hearing: Ligand-gated ion channels Touch also uses ion channels.
3. Target
   1. Receptors

      Nota:

      • Agonist and antagonist action on receptors. Directly, it affects ion channels opening/closing In transduction: It increases enzyme activation/inhibition, Modulation of how many ion channels and DNA transcription.

      Adjunto:

      • Site of Drug Action: Dose Responses
      1. Areas

         Nota:

         • Found in many locations: Transmembrane Intracellular Nucleus
      2. Types
         1. Ligand-gated ion channels

            Nota:

            • Multiple types, always sits on membrane. The ligand will bind internally or externally depending on types. Examples of ligands are: ACH, ATP, GABA, glutamate, Glycine or seratonin. One specific example is the 5 receptor subunits of the ACh receptor whereby a ligand will bind to it's side.
         2. G-protein coupled Receptors/7TM

            Nota:

            • It generally have 7 transmembrane helices. In actual fact there's a 8th Helice at the bottom. Its like a cone, top end is open while the bottom end is closed. Agents bind to the receptors and change the "tail" end and it does something.
         3. Kinase-linked receptors

            Nota:

            • 5 main types: Receptor Tyrosine Kinase (RTK): Acts and contains intrinsic kinase activity such as insulin Receptor Serine/Threonine Kinase: Contains intrinsic serine kinase activity Receptor Guanylyl Cyclase Tyrosine-kinase associated Receptors Receptor Tyrosine Phosphatases They generally are 2 separate strucutre and need to be dimerised for it to work.
         4. Nuclear receptors

            Nota:

            • Nuclear receptors are receptors that occur in the middle of the cell or within the cellular structure itself unlike the other receptors where they are all surface membrane receptors. Present in 2 classes Class one is present in the Nucleus and act as homodimers, and uses more of endocrine and steroid ligands. Has high affinity. Class II is present in the nucleus, it acts as a heterodimers, mainly lipid ligands and has low affinity.
   2. Ion Channels

      Nota:

      • Blocks/modulate action of ion channels.
   3. Enzymes

      Nota:

      • Can act as a inhibitor. False substrate to produce abnormal metabolite or as a pro-drug whereby an enzyme interact with some other thing to produce an effect.
   4. Transporters
   5. Time