Opioids Flashcards
How many types of opioid receptor are there
4
What are the names of each of the opioid receptors
MOP (mu)DOP (delta)KOP (kappa)NOP (nociceptor)
What are the downstream events of the opioid receptors
All the same. Coupled to a G[i/o] protein. Decreases adenylyl cyclase and calciumIncreases potassium
What types of receptors are ionotropic
Voltage/ligand gatedinc. GABAa
What types of receptors are metabotropic
GPCRsinc. GABAb
What is the structure of a Voltage-Activated Calcium Channel
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
Which types of voltage-activated calcium channels are involved in opioid reception
P/Q and N
How can calcium currents be recorded
Patch clamp technique. Micropipette clamps onto the region of interest. Suction. Record.Can detect whole cell or part of a cell.
What are the three types of anaesthetic
Local - close to pain source
Central - through central/spine sites
General - loss of consciousness and/or analgesia. Acts on GABA receptors.
Give some examples of opioid analgesic drugs used
Codeine
Tramadol
Morphine
Methadone/Oxycodone
How can the MOPr lead to analgesia
Inhibition of calcium channels. Present on neurones. By blocking calcium release, signal cannot reach the brain and create pain.
What effects can inhibiting opioid receptor activity have
Reduction of addictive behaviour (drugs/food/gambling etc)
How can opioid receptors influence dopamine levels
MOPr activation (specifically GAPA receptors) dis-inhibits dopamine neurons in the reward pathway.
How many types of arrestin are there
4 (arrestins 1-4)
Arrestin 2 and 3 = beta-arrestin 1 and 2..
What is the barcode hypothesis
I DONT KNOW THIS LOOK IT UP.
What are the opioid effects in vivo
Analgesia Respiratory depression Immunosuppression Constipation Hyperalgesia (pain resistance) Tolerance Reward -> addiction In rats; increased locomotion
What happens in MOR knockout mouse
None of the opioid effects are displayed. Importantly; no tolerance.
What is the molecular basis for drug tolerance
Beta-arrestin. Shown in beta-arrestin knockout mice
What happens in a beta-arrestin knockout mouse
No drug tolerance.Thought that morphine creates greater ‘reward’Reduced morphine stimulated locomotion
How many types of dopamine receptors are there
5, but two main types
D1- like (D1/5)
D2- like (D2/3/4)
What does dopamine regulate in the body
Locomotion, cognition, reward, emotions and endocrine function
Give examples of disorders that are dopamine dependent
Schizophrenia, bipolar, depression, Parkinsons, and drug abuse/dependence
Where is Dopamine synthesised
In specific neurones by tyrosine hydroxylase (TH)
Where can dopamine neurones be found
Mainly in brain pathways (with long complicated names..)
What is the difference between DA1-like and DA2-like receptors
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.
What happens in a dopamine knockout mouse
No morphine stimulated locomotionStill exhibit morphine reward (so other pathways must be involved)
What is morphine stimulated locomotion dependent on
DA1-like receptor activation of ERK
