Superfamily 1

Question 1

What is the simplest definition of superfamily 1 receptors?

Answer 1

Chemically gated (receptor operated) ion channels

Question 2

How many subunits does a receptor in superfamily 1 have?

Answer 2

Five subunits
Made up of M1, M2, M3, M4 (transmembrane alpha helices)

Question 3

Where is the agonist binding site found on this type of receptor?

Answer 3

On the extracellular N-terminal
N-terminal is frequently glycosylated

Question 4

What is the molecular structure of SF 1?

Answer 4

2nd TM alpha helix from each sub unit contributes to channel lining
Allosteric interactions between lipid bilayer and hydrophobic amino acids in 4th TM alpha helix
Cytoplasmic loop between TM3 and TM4 alpha helices

Question 5

Give an example of a SF 1 receptor

Answer 5

Nicotinic cholinoceptor

Question 6

Why are there subtypes of Nicotinic cholinoceptors?

Answer 6

Several types of alpha and beta subunits occur
Alpha 1-10 and beta 1-4
Encoded by different genes
Subunit expression varies between tissues

Question 7

Given examples of some of the pentameters in SF1

Answer 7

NMJ - 2 alpha1, 1 beta1, 1 delta + 1 other subunit
Alpha4beta2 hetero, alpha7 homo and alpha9alpha10 heteropentameters common in CNS
Alpha3beta4 hetero in autonomic ganglia
Alpha7 homo also present in endothelial immune cells

Question 8

Give a basic explanation of how Nicotinic cholinoceptors work?

Answer 8

Nicotinic receptors contain two alpha subunits, both of which must bind to a molecule of ACh in order to activate the receptor and open the channel

Question 9

Describe how the Nicotinic cholinoceptor changes shape

Answer 9

5 subunits turn slightly in relation to each other once the agonist binds
The receptor protein structure unfolds and exposes the charged upper region of the channel pore
An ion flux occurs through the channel
Altered membrane potential cause the cell excitability

Question 10

How does subunit composition and ratio change the properties of a receptor?

Answer 10

Can influence the affinity for ACh/ nicotine
Influence cation selectivity
Influence susceptibility to desensitisation
Opportunity for more diverse allosteric regulations at multiple site
Subunit mutations implicated in neurological disorders

Question 11

What therapeutic application do partial agonists selective for alpha4 beta2 heteropentameters have?

Answer 11

Smoking cessation: verenicline
Reduces acute nicotine craving when quitting
Reduces chronic Nicotinic reinforcement (pleasure reward)

Question 12

What therapeutic effects do antagonists selective for alpha9 alpha10 heteropentameters have?

Answer 12

Subcutaneous / intramuscular administration
Acutely alleviate pain resulting from traumatic, inflammatory or metabolic neuronal injury

Question 13

What therapeutic benefits do +ve allosteric modulators at alpha7 containing pentameters have?

Answer 13

Attenuate cognitive decline in dementia

Question 14

What does galantamine treat and why is described as multi target?

Answer 14

Alzheimer’s
Acts as a nAChR allosteric modulator and a cholinesterase inhibitor

Question 15

What does bupropion treat and why is it described as multi target?

Answer 15

Smoking cessation and depression
Acts as a nAChR allosteric modulator and a monamine re-uptake inhibitor

Question 16

What does carbamazepine used for and why is it described as multi target?

Answer 16

Anticonvulsant
Acts as a nAChR allosteric modulator and a voltage gated sodium channel blocker

Question 17

Give a 2nd example of an SF1 receptor

Answer 17

GABA A receptor / chloride channel

Question 18

Describe SF1 GABA A receptors

Answer 18

A family of receptors for inhibitory neurotransmitter gamma aminobutyric acid (GABA)
Widely distributed in the CNS

Question 19

Give a basic explanation of how diazepam works

Answer 19

Targets GABA A receptors as a positive allosteric modulator

Question 20

What is the molecular structure of GABA A?

Answer 20

2 alpha, 2 beta and 1 gamma/theta/pi/lambda subunit

Question 21

How does the GABA A receptor react/ interact?

Answer 21

Convulsants (picrotoxin) block channel pore
Cytoplasmic loop between TM3 and TM4 alpha helices of beta subunit subject to phosphorylation
Allosteric regulation by general anaesthetics, ethanol, neuro steroids
Lipid bilayer exerts direct allosteric interaction

Question 22

How does the opening of GABA A Cl- channels alter the body?

Answer 22

Drugs that open the chloride channels are called positive allosteric modulators
They have a CNS depressant action, sedative and anxiolytic effects

Question 23

Give examples of drugs that act on the GABA A receptor

Answer 23

Barbiturates
Propofol
Benzodiazepines
Alcohol

Question 24

Define what an overdoes is

Answer 24

The excessive stimulation of GABA A chloride channels

Question 25

What happens during an overdose?

Answer 25

Usually seen in combination with alcohol/ alcoholism
Coma, respiratory depression, may result in death

Question 26

What is strychnine an example of?

Answer 26

A glycine receptor
Chloride channel

Question 27

Describe strychnine

Answer 27

Is a receptor antagonist
Neurotoxic to motor nerves in the spinal cord (excitatory effect)
Used as a pesticide to kill small rodents by muscle spasm, convulsions, choking, respiratory arrest

Question 28

Give an example of a serotonin SF 1 receptor

Answer 28

Serotonin 5-HT3 receptor
Cation (sodium/potassium) channel
Distinct from other non SF1 serotonin receptors