Lecture 3 - Receptor mechanism I

Question 1

Receptor properties (4)

Answer 1

Intra/Extracellular communication
Tissue selectivity
Chemical selectivity
Amplification

Question 2

Specific sequences of amino acids compose… (3)

Answer 2

Selectivity of drug bound.
Type of intracellular pathway activated.
Timescale of information transfer (ms to days).

Question 3

Analgesic

Answer 3

(of a drug) acting to relieve pain.

Question 4

Enzymes (2)

Answer 4

Sildenafil (erectile dysfunction) - blocks PDE-5.

Aspirin (analgesic) - blocks COX.

Question 5

Carrier molecules (3)

Answer 5

o Diuretics – inhibits Na+/K+/Cl- carriers and Na+ reuptake in kidney.
o Digoxin - inhibits Na+/K+ ATPase, used atrial fibrillation.
o Fluoxetine - blocks serotonin uptake, anti-depression.

Question 6

Ion channels (2)

Answer 6

o Local anaesthetics, e.g. lignocaine - ‘plugs’ Na+ channel pore.
o Anti-hypertensives, e.g. Ca2+ channel blockers.

Question 7

Ligand-gated receptors (6)

Answer 7

5 protein subunits - 4.
Ligand binding site on N terminal region.
Extracellular site.
Forms an ion channel.

e.g.
Nictonic - Skeletal muscle contraction
Glutamate - Action potentials in the brain.

Question 8

Signal transduction mechanism (8)

Answer 8

Ligand binds to receptor –> Conformation change in subunits ion channel opens –> increase ion flux –> change in cell excitability.
Takes millilseconds (ms).
Cell excitability
+ve into cell = depolarisation = excitation.
-ve into cell = hyperpolarisation = inhibition.
Nic/Glutamate/5HT3 receptor - Na influx - excitation - depolarisation
GABAa/Glycine receptors - Cl influx - inhibition - hyperpolarisation.

NMJ, ACh binds to nicotinic receptors.

Question 9

Ligand gated ion channel and agonists (stimulates them) (4)

Answer 9

Nicotinic cholinoreceptor = ACH
5HT3 = 5-HT.
GABAA = GABA (y amino butyric acid)
Glycine = Glycine

Question 10

Nicotinic type ACh receptors (4)

Answer 10

Skeletal muscle end platers

• N1/NM
• N1 = Muscle nictonic AChR in skeletal muscle contracts quickly.
• Adult neuromuscular junction = a1-e-a1-b1-d
• Foetal extrajunctional = a1-g-a1-b1-d

CNS

• N2/NN
• N2 = Neuronal nicotinic AChRs a2-a8 b2-b4.

Question 11

Myasthenia gravis (4)

Answer 11

Chronic autoimmune disease.
Causes weakness in the skeletal muscles, responsible for breathing and moving parts of the body.
Muscle nicotinic AChRs become degraded.
Targets a1 subunit, brain is unaffected (does not contain a1).

Question 12

Myasthenia gravis - symptoms (5)

Answer 12

o	Muscle weakness
o	Drooping eyelids
o	Fatigue
o	Difficulty swallowing or talking
o	Exertion is difficult

Question 13

Myasthenia gravis - graph (2)

Answer 13

Normal – membrane has ripples called mepps (Miniature end-plate potential).
Caused by depolarisation the body is never quite constantly, ACh receptors is colliding with the membrane, little ACh is spilling out with reacts with its receptors leaving us with a meep on the graph.

Question 14

Stimulation of GABAA receptors in neurones inhibits activity quickly (4)

Answer 14

Inhibitory nerves release GABA/Glycine.
GABAA/Glycine LGIC allow Cl- ions to enter = hyperpolarisation = inhibition = more -ve.
Hyperpolarises major pathways in the brain.
Fast response as there are different receptors with the same structure (all LGIC have same structure).