Lecture 10: Introduction to Metabotropic Receptors

Question 1

List the three ways metabotropic receptors modulate ion channels.

Answer 1

1. Coupling by g protein directly to an ion channel to alter its permeability
2. Coupling by g protein to a second messenger system where the second messenger (e.g. cAMP, cGMP) directly regulates an ion channel
3. Coupling by g protein to a second messenger system, leading to an ion channel phosphorylation i.e. activation of a kinase

Question 2

Effect of G alpha s

Answer 2

Stimulation of adenylyl cyclase which activates protein kinase A

Question 3

Effect of G alpa i

Answer 3

Inhibition of adenylyl cyclase

Question 4

Effect of G alpha q

Answer 4

Stimulation of phospholipase C

Question 5

Effect of G alpha t (the alpha subunit of transducin, the g protein associated with rhodopsin)

Answer 5

Stimulation of cGMP PDE (phopshodiesterase), reducing cGMP levels.

Question 6

Function of adenlyl/adenylate cyclase

Answer 6

Adenlyl cyclase is a g protein activated effector and enzyme that converts ATP to cAMP

Question 7

Activation of phospholipase C causes…

Answer 7

PLC catalyses the hydrolysis of the phospholipid (PIP2) yielding DAG and an intermediate which is converted to IP3. IP3 diffuses into the cytosol and triggers calcium release from the smooth ER to activate Ca2+/calmodulin-dependent protein kinase II. DAG on the other hand, remains fixed in the plasma membrane and activates protein kinase C.

Question 8

True or false:

Peptide neurotransmitters have metabotropic and ionotropic receptors.

Answer 8

False, peptide neurotransmitter receptors are all metabotropic.

Question 9

True or false:

Peptide neurotransmitters are recycled at the nerve terminal.

Answer 9

False, peptide neurotransmitters are endocytosed and transported back to the cell body. They are not recycle.

Question 10

Vesicles containing peptide transmitters are called…

Answer 10

Large Dense-Core Vesicles (LDCV) which are 200-400 nm in diameter

Question 11

Neuropeptide Y has several functions including….

Answer 11

lowering blood pressure, appetite stimulation, and storage of energy as fat, reducing anxiety and stress, reducing pain perception, affecting the circadian rhythm, reducing voluntary alcohol intake, lowering blood pressure, and controlling epileptic seizures.

Question 12

Function of neuromodulators

Answer 12

Alter the excitability of the post-synaptic neuron, but don’t regulate the membrane voltage directly

Question 13

Function of co-transmitters

Answer 13

An example of neuromodulatory action, but released from the same synapse as a fast neurotransmitter.
Often contain two vesicles: small molecule vesicle (usually glutamate) and a peptide containing vesicle.

Question 14

Function of autoreceptors

Answer 14

Present on the pre-synaptic terminal, they inhibit release of neurotransmitter. These are presynaptic - negative feedback effect.
Binding to an autoreceptor inhibits voltage-activated calcium channels
Therefore release of neurotransmitter is also inhibited

Question 15

True or false:

Ionotropic and metabotropic receptors are clustered tightly within the PSD.

Answer 15

False. Metabotropic receptors are more spread out.
Their PSDs are less dense.
Some receptors lie outside the PSD.

Question 16

Outline the process of GPCR desensitisation.

Answer 16

Activation of g protein activates a kinase which phosphorylates a g protein receptor kinase (GRK) which in turn phosphorylates the GPCR.
A GRK only phosphorylates the GPCR while the GPCR has a ligand bound to it.
The phosphorylation sites interfere with g protein coupling.
Enough phosphorylation causes arrestin to bind which stops g protein activation. Arrestin, as well as interfering with g protein coupling also causes clumping of arrestin-bound GPCRs and subsequent internalisation of the GPCRs via endocytosis.

Question 17

Which types of neurotransmitters are metabotropic?

Answer 17

The catecholamines including dopamine, epinephrine and norepinephrine and the peptide neurotransmitters.
Ionotropic neurotransmitters can also be metabotropes, e.g. acetylcholine (muscarinic receptors), glutamate (mGluR), GABAb receptor