RECEPTORS

RECEPTORS

1. Super Families of Receptor Proteins

   • Plasma Membrane
     • ligand gate ion channels
       • eg nicotine and acetyl choline receptors
     • G Protein coupled receptors
       • aka signal proteins structure: 7 helices with N terminal on outside
       • Binding site on inside usually closed, ligand binding causes conformational change to open this
       • G protein (alpha beta & gamma) binds to inner bindng site
         • Alpha usually has GDP (guanosine diphospate) which is then replaced GTP on activation
           • Gamma and beta separate
             • alpha inactivated when its own phosphoryating GTPase or protein phosphotase activity turn GDP to GTP
               • G protein subunits recombine and attach to cell membrane
       • alpha activates adenylate cyclase to produce cyclic AMP
         • (secondary messenger) can go on to activate protein kinase A which activates phosphorylation of theorine and serine in other enzymes( glycogen to glucose)
       • DRUGS
         • Beta adrenergic receptors switched on by adrenaline
           • B1 open calcium channels
           • B2 close channels - asthma - relaxing smooth muscles
         • Muscuranic receptors -cholinergic receptors on smooth muscles and cardiac tissue
           • agonists switching on GI after surgery
           • antagonists close GI after surgery
           • shaking in parkisons
     • tyrosine kinase receptors
     • contain intra, extra & transcellular membrane
   • cytosolic intracellular
     • nucleur hormone receptors
       • involved in every major organ and metabolic system eg bone, muscle, hormone mediated cancer, homeostasis, sexual and embryonic development
       • 2. binds receptor- conformational change
       • 1. ligand crosses membrane
       • 3. dimerisation
       • 4. proteinsythesis
       • 5. binds to coactivator protein
       • 6. complex transloacates to nucleus and binds to specific region of DNA
         • initiates transcription- directly involved in gene expression
       • single protein steroid binding region near C terminal and DNA binding region near N terminal
         • DNA binding region = zinc fingers 9 cysteine residues, 8 contain zinc to stabilise structure
           • dimer- both need to be activated- identifies particular nucleuotide sequence
       • for steroids and thryroid
       • DRUGS
         • Glucocorticoid receptor: using adrenal gland extracts (cortisone) for allergy treatment. Abused by athletes.
         • Progesterone Receptor: control ovulation
         • Oestrogen receptor: using oestradiol for fertility control and breast cancers
           • oestrodiol = steroid effect growth and development
             • H12 folds across binding site which then exposes Activation Function AF2 (hydrophobic) after step two
           • Tamoxifen for breast cancer- prevents binding of oestrogen to its receptor
   • can be classified based on pharmacological activity (drug/ligand) nature here classified by structural pathway

2. Signal transduction process

   • Receptors = proteins receive endo/exodogenous signals
     • including hormones, neurotransmitters, local chemical mediators eg prostaglandins
   • Bind with high affinity, causing conformational change
   • Chemical signal transferred to intra cellular message

3. Drugs & Receptors

   • ANTAGONIST
     • competitive or non competitive
       • binds to receptor but does not exert effect on cell
   • AGONIST
     • partial or full
       • exerts effect on cell

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