Metabotropic receptors

Question 1

explain the process of metabotropic receptors

label neurotransmitter, receptor, g protein, effector

what is the 1st messenager and 2nd messenger

Answer 1

• G-protein coupled receptor (GPCR)
• G-proteins: guanine nucleotide-binding protiens
• act as molecular switches
• when bound ot GTP = they are ‘on’
• when bound to GDP = they are ‘off’
• neurotransmitter is the 1st messenger
• G-protein acts on effecotr portein and sends a 2nd messenger to target

Question 2

What is the structure of a G-protein coupled receptor

how much transmembrane domains and how does it bind

Answer 2

• 7 transmembrane domains (TM1-7)
• G-protein generally binds to T5-T7 region, but sometomes includes T3 and/or T4

Question 3

What is the structure of the G-protein

Answer 3

• alpha, beta, gamma subunit
• GDP bound to alpha subunit (off)
• GDP is exchanged with GTP (ON)
• G- protein separates into alpha and beta/gamma subunits

Question 4

How does the G-protein act on ACh at heart vs the gut

Answer 4

heart
- K+ flows out of cell causing IPSPs (hyperpolarization)
- heart rate decreases
gut
- K+ channels close and cause a excitiation (depolarization)

Question 5

Explain how G-protein works with norepinephrine

Answer 5

• alpha subunite activates adenylate cyclase
• converting ATP to cyclic AMP and activates proetin kinases that phosphorylates
• opening or closing ion channel proteins
• cytoplasmic proteins (activate some or inactive)
• nuclear proteins (gene expression)

Question 6

Explain what happens with Rhodospin

Answer 6

• activated rhodopsin stimulates a G protein transucin, GTp replaces GDP which releases the alpha subunit, activates cGMP phosphodiesterase
• phosphodiesterase catalyzes the breakdown of cGMP to 5’-GMP
• as the cGMP concentration decreases, cGMP detatches from Na+ channel and closes

Question 7

Explain the C pathway

PIP2, IP3 and DAG

Answer 7

• alpha subunit activates phospholipase C, which cleaves the mebrane phospholipid PIP2 into 2 second messengers
• DAG: activates protein kinase C: phosphorylation of regulaotry protiens
• IP3: opens Ca2+ channels by binding to ion channel in rough ER
• Ca2+ acts as a 2nd messenger; enhances activation of protein kinase C by binding with Calmodulin

Question 8

Define presynaptic inhibition

Answer 8

• decreases amount of neurotransmitter released by the pre-synatpic axon and decrease the size of PSP in the post-synatic neuron

Question 9

Define presynatpic facilitation

Answer 9

• increases amount of neurotransmitters = increases the size of PSP in post-synaptic neuron

Question 10

What is an example of a presynaptic facilitation

serotonin

Answer 10

• serotonin acts on cAMP to close K= channels = prevent repolarization = prolonged action potential
• Ca2= open for longer increasing the release of neurotransmitter

Question 11

What is an exmaple of presynaptic inhibition

GABA and GABAA/ GABAB

Answer 11

1. GABAA
   - opening of Cl- channels = influx = decrease size of action potential = reduces Ca2+ entry and the relase of neurtransmitter = smaller PSP
2. GABAB
   - open K+ channels = efflux = reduce size of action pential = decrease in Ca2+ influx
   - cAMP can inhibit Ca2+ channels directly