Introduction to Pharmacology and Toxicology- Transporters as targets

Question 1

What membranes does passive diffusion require?

Answer 1

Doesn’t require any proteins

Example: glycerol- no membrane needed to diffuse across

Question 2

What membranes does facilitated diffusion require?

Answer 2

Requires a protein, substance flows along concentration gradient
Example: Glucose transporters- to and from the brain- blood brain barrier

Question 3

What membranes does Primary Active Transport require?

Answer 3

Requires a protein which a substance flows against concentration gradient

This requires energy to provide directly by ATP hydrolysis- Na+K+ATPase- transfers multiple ions

Question 4

What membranes does Secondary Active Transport require?

Answer 4

Requires a protein where substance flows against concentration gradient

Energy required provided indirectly by ATP hydrolysis
Gradient of ion used to couple transport (usually sodium)

Can be simper or antiport mechanism
Can go forward or backward

Question 5

What does it mean by facilitated transport is saturated?

Answer 5

Can only have as much substrate on the extracellular domain, cannot transport anymore of that ion or that molecule due to the levels of substrate concentration

Need active transport to solve the issue

Question 6

What are the different classes of pumps?

Answer 6

1. P class pumps
2. V class pumps
3. F class pumps
4. ABC (ATP binding cassete)

Question 7

What is the function of the P class pump work and what does it transport?

Answer 7

1. Transports all types of ion- phosphorylation event occurs
2. Only specific to one or two kinds of ions
3. Transport more than one type of ion at a time
4. Example: Na+/K+ pump

Question 8

What is the function of the V class Pump and what does it transport?

Answer 8

1. Only transports protons
2. Structure is very different to P class
3. They are normally used to maintain a low pH in vacuoles and Lysosomes

Question 9

What is the function of the F class pump and what does it transport?

Answer 9

1. Only transports protons down its electrochemical gradient, using the movement of protons to power ATP synthesis
2. Structure is very different to F class
3. Example: ATP synthase pump found in mitochondria

Question 10

What is the function of the ABC (ATP Binding Cassette) and what does it transport?

Answer 10

1. Superfamily of pumps that can transport all kinds of molecules- including polysaccharides and proteins
2. All pumps contain two transmembrane domains and two cytosolic domains which bind ATP
3. Example: CFTR pump in the membrane of epithelial cells can cause cystic fibrosis if mutated

Question 11

What are the different 3 transporter families?

Answer 11

1. Ion transporters and pumps- sodium potassium ATPase
2. Metabolite transporters
3. Neurotransmitter Transporters
   - vascular
   - plasma membranes

Question 12

What are the metabolite transporters and give an example?

Answer 12

1. Drug super family of transporters
2. Chloroquine Resistance Transporter (PfCRT) Family:
   some malarial parasites have developed resistance to chloroquine through mutations in this transporter

Question 13

What are the Neurotransmitter transporters I?

Answer 13

1. Vesicular inhibitory amino acid transporter
2. Vesicular excitatory amino acid transporter
3. Vesicular amine transporters

Used for scientific research for things to be packed into vesicles and released into the synaptic terminal

Packaging neurotransmitter for release

Question 14

What are the neurotransmitter transporters II used for? And give some examples

Answer 14

In the plasma membrane that's tailored to specific transporters
NET- Noradrenaline transporter
DAT- dopamine transporters
5-HT Transporters
EAAT- Excitatory amino acid transporters
GAT- GABA transporters
GlyT- Glycine transporters

Question 15

How does the pre synaptic terminal and post synaptic terminal work?

Answer 15

The presynaptic terminal sends a signal of serotonin containing vesicle through the serotonin transporter/5-HT transporter

Question 16

How does the 5-HT+ transporter works?

Answer 16

For one K+, one Na+ and Cl- comes along

Question 17

What does serotonin do?

Answer 17

Creates happy thoughts

Question 18

What does citalopram do?

Answer 18

1. Blocks serotonin reuptake (member of the SSRIs)
2. More increase of serotonin signal so it stays longer
3. Indication: Depressive illness, panic disorder

Question 19

What does the dexamfetamine do?

Answer 19

1. Blocks monoamine transporters (including the dopamine family)
2. Stimulant that increase the levels of central nervous system stimulate
3. Indication: narcolepsy, refractory attention deficit, hyperactivity disorder

Question 20

What does cocaine do?

Answer 20

Bind to the dopamine transporter and acts as an antagonist

Question 21

What does Riluzole do?

Answer 21

1. Reduces glutamate “excitotoxcity” via multiple interactions
2. One target is the EAATS where suggests an up regulation of transporter proteins
3. Indication: extend life of patients with amyotrophic lateral sclerosis
   - initiated by specialists experienced in the management of motor neurone disease