Receptors and transduction mechanisms II • Chapter 12 – The Neuron by Levitan and Kacsmarek
Jan 16, 2016
Receptors and transduction mechanisms II
• Chapter 12 – The Neuron by Levitan and Kacsmarek
Glutamate Class1 ClassII ClassIII
GABAB Dopamine Acetycholine (muscarininc)
5-HT histamine
mGluR1 mGluR2 mGluR4 GABABR1 D1A M1 5-HT1 H1 mGluR5 mGluR3 mGluR6 GABABR2 D1B M2 5-HT2 H2
mGluR7 D2 M3 5-HT3 H3 mGluR8 D3 M4 5-HT4 D4 M5 5-HT5 5-HT6 5-HT7
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
SLOWINDIRECT
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 epinephrineTMV – two Ser (S204 +S207) binds to 2 OH termini
Intracellular signal transduction by the PIP2 cascade
mGluR1/5
Homer
Ca2+
IP3R
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 265-272
Nature Reviews Drug Discovery 4, 131-144 (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 114-120
Residues that control the coupling of metabotropic glutamate (mglu) receptors to G proteins
Human -adrenergic receptor
TMIII – Asp (D113) binds to N-terminus of epinephrineTMV – two Ser (S204 +S207) binds to 2 OH termini
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.
SLOWINDIRECT
Metabotropic receptors (G-protein-coupled receptors, GPCR
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