PH2113 - Neuropharmacology 4

Question 1

What is the structure of the ionotropic receptor?

Answer 1

Membrane pore
4 transmembrane spanning helices
Channel made up of 5 subunits
M2 subunit lines the pore
Charged amino acids at the top and bottom create the selectivity
A ring of leucines for the 'gate'
- closed in the absence of a ligand
- determine the pore size
- determines the size of the ion that passes through

Question 2

What can ligand-gated ion channels be affected by?

Answer 2

Agonists
- ligand
Antagonists
Channel blockers
Allosteric modulators

Question 3

What are the features of nicotinic acetylcholine and 5-HT3 receptors?

Answer 3

Na+/K+

Stimulatory

Question 4

What are the features of GABA receptors?

Answer 4

Cl-

Inhibitory

Question 5

What are the current or potential therapeutic applications of acetylcholine receptor active compounds?

Answer 5

Tobacco addiction
- varenicline/bupropion
General anaesthetics
Alzheimer's disease
Parkinson's disease
Schizophrenia
ADHD
Neuropathic pain

Question 6

Give examples of therapeutic applications of 5-HT3 receptor modulators

Answer 6

Agonists may alter mood
- varenicline
- lamotrigine maybe inverse agonist
Antagonists
- nausea and vomiting
- chemotherapy
- radiotherapy
- post-surgical
- post-operative neuropathic pain
- headache and migraine

Question 7

What is the structure of the GABA receptor?

Answer 7

5 subunits

• 2 alpha
• 2 beta
• 1 gamma

Question 8

What are the two types of L-glutamate receptor?

Answer 8

NMDA receptor
non-MDA receptor
- AMPA
- kainate

Question 9

What is the function of the AMPA glutamate and kainate receptor?

Answer 9

Fast synaptic excitation

Question 10

Which diseases can be caused by faulty NMDA receptors?

Answer 10

Alzheimer's
Parkinson's
Huntington's
Schizophrenia
Epilepsy
Encephalitis
Stroke

Question 11

Give an example of an agonist for an NMDA receptor

Answer 11

Glutamate
Aspartate
NMDA

Question 12

Give an example of an antagonist for an NMDA receptor

Answer 12

D-AP5

Question 13

What effect does having variable subunits have on a receptor structure?

Answer 13

Diversity of channels
Different ligand binding affinities
- AMPA vs kainate
Differential expression in specific regions
Developmental changes
- nACh
Differential permeability to ions
- AMPA vs kainate
Greater opening of the channel
- AMPA receptor

Question 14

What effect does having different types of pharmacological regulators have?

Answer 14

Direct binding
- competitive agonists/antagonists
Indirect binding
- non-competitive agonists/antagonists
Ion channel blockers
Allosteric modulation

Question 15

What is a metabotropic receptor?

Answer 15

G-protein coupled receptor

Question 16

What is the function of a metabotropic receptor?

Answer 16

Mediate cellular response to neurotransmitters or hormones

Directly responsible for senses of sight, smell and taste

Question 17

What are the two classes of metabotropic receptors?

Answer 17

Rhodopsin-like 7-transmembrane segment

Secretin receptors

Question 18

What are the properties of rhodopsin-like 7-transmembrane segment receptors?

Answer 18

Largest group
- > 300
Family 1
- family A
Receptors for more transmitters
Short extracellular N terminal

Question 19

What are the properties of secretin receptors?

Answer 19

Approximately 34
Family 2
- family B
Receptors for peptide hormones
Ligand binding on intermediate extracellular tail

All have a hormone binding domain and bind peptide hormones

Question 20

What is rhodopsin?

Answer 20

Photopigment in rods

Question 21

Give four examples of hormones used to target secretin receptors?

Answer 21

Calcitonin
- hypercalcaemia
Glucagon
- hypoglycaemia
GLP-1a
- glucose regulation
Parathyroid hormone
- osteoporosis