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

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Receptors and transduction mechanisms II Chapter 12 –The Neuron by Levitan and Kacsmarek

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 Metabotropic receptors (G-protein-coupled receptors, GPCR)

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

SLOW INDIRECT 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

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

Generic GPCR structure Why 7TMs?

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

Intracellular signal transduction by the PIP2 cascade

mGluR1/5 Homer Ca 2+ IP 3 R

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

Responses can be regulated by altering receptor numbers

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

Some types of GPCR

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

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

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

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

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

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. 2) Second messenger-mediated receptor-channel coupling: an intracellular second messenger influences ion channel activity. 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.