Opioids

Question 1

How many types of opioid receptor are there

Answer 1

4

Question 2

What are the names of each of the opioid receptors

Answer 2

MOP (mu)
DOP (delta)
KOP (kappa)
NOP (nociceptor)

Question 3

What are the downstream events of the opioid receptors

Answer 3

All the same. Coupled to a G[i/o] protein.
Decreases adenylyl cyclase and calcium
Increases potassium

Question 4

What types of receptors are ionotropic

Answer 4

Voltage/ligand gated

inc. GABAa

Question 5

What types of receptors are metabotropic

Answer 5

GPCRs

inc. GABAb

Question 6

What is the structure of a Voltage-Activated Calcium Channel

Answer 6

24 TM proteins split into 4 helices. Voltage activation occurs in the fourth helix.
Composed of alpha 1 (24TM); alpha 2; beta; gamma and delta subunits

Question 7

Which types of voltage-activated calcium channels are involved in opioid reception

Answer 7

P/Q and N

Question 8

How can calcium currents be recorded

Answer 8

Patch clamp technique.
Micropipette clamps onto the region of interest. Suction. Record.
Can detect whole cell or part of a cell.

Question 9

What are the three types of anaesthetic

Answer 9

Local - close to pain source
Central - through central/spine sites
General - loss of consciousness and/or analgesia. Acts on GABA receptors.

Question 10

Give some examples of opioid analgesic drugs used

Answer 10

Codeine
Tramadol
Morphine
Methadone/Oxycodone

Question 11

How can the MOPr lead to analgesia

Answer 11

Inhibition of calcium channels. Present on neurones. By blocking calcium release, signal cannot reach the brain and create pain.

Question 12

What effects can inhibiting opioid receptor activity have

Answer 12

Reduction of addictive behaviour (drugs/food/gambling etc)

Question 13

How can opioid receptors influence dopamine levels

Answer 13

MOPr activation (specifically GAPA receptors) dis-inhibits dopamine neurons in the reward pathway.

Question 14

How many types of arrestin are there

Answer 14

4 (arrestins 1-4)

Arrestin 2 and 3 = beta-arrestin 1 and 2..

Question 15

What is the barcode hypothesis

Answer 15

I DONT KNOW THIS LOOK IT UP.

Question 16

What are the opioid effects in vivo

Answer 16

Analgesia
Respiratory depression
Immunosuppression
Constipation
Hyperalgesia (pain resistance)
Tolerance
Reward -> addiction
In rats; increased locomotion

Question 17

What happens in MOR knockout mouse

Answer 17

None of the opioid effects are displayed.

Importantly; no tolerance.

Question 18

What is the molecular basis for drug tolerance

Answer 18

Beta-arrestin.

Shown in beta-arrestin knockout mice

Question 19

What happens in a beta-arrestin knockout mouse

Answer 19

No drug tolerance.
Thought that morphine creates greater ‘reward’
Reduced morphine stimulated locomotion

Question 20

How many types of dopamine receptors are there

Answer 20

5, but two main types
D1- like (D1/5)
D2- like (D2/3/4)

Question 21

What does dopamine regulate in the body

Answer 21

Locomotion, cognition, reward, emotions and endocrine function

Question 22

Give examples of disorders that are dopamine dependent

Answer 22

Schizophrenia, bipolar, depression, Parkinsons, and drug abuse/dependence

Question 23

Where is Dopamine synthesised

Answer 23

In specific neurones by tyrosine hydroxylase (TH)

Question 24

Where can dopamine neurones be found

Answer 24

Mainly in brain pathways (with long complicated names..)

Question 25

What is the difference between DA1-like and DA2-like receptors

Answer 25

DA1- like activate adenylate cyclase (involved in ERK/RAF/MEK; and lead to ERK1/2 activation)
DA2-like inhibit adenylase cyclase (involved in PP2A/AKT; lead to GSK3 inhibition)
They have very different signalling pathways.

Question 26

What happens in a dopamine knockout mouse

Answer 26

No morphine stimulated locomotion

Still exhibit morphine reward (so other pathways must be involved)

Question 27

What is morphine stimulated locomotion dependent on

Answer 27

DA1-like receptor activation of ERK