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Receptors and transduction mechanisms II

Receptors and transduction mechanisms II. Chapter 12 The Neuron by Levitan and Kacsmarek. Metabotropic receptors (G-protein-coupled receptors, GPCR. Metabotropic receptors (G-protein-coupled receptors, GPCR).

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Receptors and transduction mechanisms II

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  1. Receptors and transduction mechanisms II • Chapter 12 • The Neuron by Levitan and Kacsmarek

  2. Metabotropic receptors (G-protein-coupled receptors, GPCR

  3. Metabotropic receptors (G-protein-coupled receptors, GPCR) IN the case shown here, binding of neurotransmitter (NT) to its receptor activates a G protein that then interacts with an ion channel, causing it to open

  4. Second messenger-mediated receptor-channel coupling an intracellular second messenger influences ion channel activity

  5. GPCR coupling These receptors are not directly coupled to their ion channels and transduce the signal via guanyl nucleotide-binding proteins (G-proteins) that activate intracellular second messenger pathways SLOW INDIRECT

  6. Why are GPCR responses slower and longer lasting than iR responses? Allows a constant modification temporal information processing

  7. Generic GPCR structure Why 7TMs?

  8. Human b-adrenergic receptor TMIII – Asp (D113) binds to N-terminus of epinephrine TMV – two Ser (S204 +S207) binds to 2 OH termini

  9. Intracellular signal transduction by the PIP2 cascade

  10. mGluR1/5 Homer IP3R Ca2+

  11. GPCR coupling can produce diverse responses • Depends on type of G-protein and type of effector • Single ligand can activate multiple GPCR pathways • Depends on receptor numbers

  12. Responses can be regulated by altering receptor numbers

  13. Desensitisation is a mechanism of decreasing the cellular response to transmitter Desensitisation is defined as the increase in agonist required to produce ahalf-maximal stimulation of effector Physical removal by receptor-mediated endocytosis Brought about by receptor phosphorylation

  14. Some types of GPCR

  15. group I, II and III metabotropic glutamate (mGlu) receptors Trends in Pharmacological Sciences Volume 25, Issue 5 , May 2004, Pages 265-272

  16. Nature Reviews Drug Discovery 4, 131-144 (2005) Metabotropic glutamate receptors as novel targets for anxiety and stress disorders

  17. neurotransmitter pathways implicated in mediating the actions of drugs of abuse (rat brain)

  18. Residues that control the coupling of metabotropic glutamate (mglu) receptors to G proteins A metabotropic glutamate (mglu) receptor associated with a heterotrimeric G protein Trends in Pharmacological Sciences Volume 22, Issue 3 , 1 March 2001, Pages 114-120

  19. group I, II and III metabotropic glutamate (mGlu) receptors neurotransmitter pathways implicated in mediating the actions of drugs of abuse (rat brain)

  20. 1) G protein-mediated receptor-channel coupling. IN the case shown here, binding of neurotransmitter (NT) to its receptor activates a G protein that then interacts with an ion channel, causing it to open. 3) With second messenger coupling the binding of a single transmitter can activate many channels, activate several classes of channels and affect other cellular processes not associated with ion channels. 2) Second messenger-mediated receptor-channel coupling: an intracellular second messenger influences ion channel activity.

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