Topic 1: Cell Communication [2-5]

Question 1

What is the cell-to-cell junction called that join adjacent cells and is used for small soluble signals?

Answer 1

Gap junctions

Question 2

How do a) Hydrophobic (1 way) and b) Hydrophilic (4 ways) molecules cross membranes?

Answer 2

a) Free diffusion
b) - Pumps / transporter
- ion channel
- vesicle fusion / fission (exo/endocytosis)
- indirectly, receptors & signalling pathways

Question 3

Name some examples of signalling molecules

Answer 3

• proteins
• peptides
• amino acids
• nucleotides
• steroids (free diffusion)
• fatty acids
• ions
• gasses (free diffusion)

Question 4

Ionic signals and signals released via exocytosis can be released either constitutively or evoked. What do these terms mean

Answer 4

Constitutive - passive flow down the concentration gradient

Evoked - channels can be gated

Question 5

Secreted molecules mediate 4 forms of signalling, what are they and what are they used for (hint = paracrine etc)

Answer 5

Paracrine signalling: Only affect cells in the immediate environment. The signal is terminated by:

• Uptake into neighbouring cells
• Destruction by extracellular enzymes
• Sequestration by ECM

Autocrine signalling: Similar to paracrine but is confined to a specific cell type

Synaptic signalling: a specialised subtype of paracrine signalling

Endocrine signalling: secretion of hormones into the blood. Specificity maintained by only target cells having adequate receptors

(Signals that use gap junctions or gases do not need receptors)

Question 6

Specificity of signalling can be achieved by either Synaptic signalling or Endocrine signalling. Compare these two methods

Answer 6

Synaptic:
- Arises from the physical location of the signalling site and the receptor
- Therefore, diversity of neurotransmitters is small
- Short distance (the synapse itself)
- Fast
- Receptors are low affinity

Endocrine:
- Arises from the combination of different signalling molecules being recognised by many different receptors
- Therefore a wide range of signals + receptors are needed
- Long distance
- Slow
- Receptors are high affinity

Question 7

Match the type of receptor to the function:

a) Generate new signals inside the cell (second messengers)
b) Allow flow of ions across membranes
c) Modify existing molecules to generate new signals
d) Changes expression of genes

• Steroid
• Ionotropic
• Kinase
• Metabotropic

Answer 7

a) Metabotropic
b) Ionotropic
c) Kinase
d) Steroids

Question 8

Name the two types of ionotropic receptor and the types of ions they effect

Answer 8

Excitatory - Influx of positive ions
Inhibitory - Influx of negative ions

Question 9

What is the general function of metabotropic (G-protein-linked) receptors?

Answer 9

They act indirectly to regulate the activity of a plasma-membrane-bound target protein such as an enzyme or an ion channel.

The intermediate between the receptor and the target is a trimeric G-protein

Question 10

What happens when a ligand binds a metabotropic receptor i.e. it is activated (in relation to the alpha, beta and gamma subunits)

Answer 10

Ligand binding causes the ALPHA subunit to release GDP for GTP causing:
1) Activation of the ALPHA-subunit
2) Release of the BETA/GAMMA-subunits

Question 11

Ligand binding to a metabotropic receptor causes a series of changes such as a) ALPHA-subunit activation and b) BETA/GAMMA-subunit release. How do these above changes affect the cell

Answer 11

a) Activation of the ALPHA-subunit alters enzyme activities and changes concentration of intracellular signals (2nd messengers)

b) Release of BETA/GAMMA-subunits sometimes causes modifications to ion channel activity

Question 12

How is signalling from metabotropic receptors terminated

Answer 12

Hydrolysis of GTP to GDP

Question 13

Kinase receptors are either enzymes themselves or associated with enzymes. Most have a transmembrane domain with a ligand binding site outside the cell and enzyme activity inside the cell.

What happens when a ligand binds a kinase receptor (in relation to phosphorylation)?

Answer 13

1) Kinase receptors phosphorylate themselves
2) Their signal is amplified via a series of phosphorylation reactions
3) Signals are terminated via the action of phosphatases

Question 14

How do steroid receptors work

Answer 14

1) Steroids freely diffuse across the plasma membrane
2) Once inside they bind to intracellular receptors, activating them
3) All steroid receptors bind to specific DNA sequences
4) Ligand binding activates gene transcription causing a 2 step response
5a) Direct transcription of a small number of genes
5b) These genes activate other genes and produce a secondary response

Question 15

How fast are the 4 receptors response times (relatively) and what are they limited by

Answer 15

Ionotropic - Very fast. Limited by:
- receptor pore size
- diffusion gradient

Metabotropic - Relatively fast. Limited by:
- number of enzymatic reactions in the cell

Kinase - Relatively fast. Limited by:
- number of enzymatic reactions in the cell

Steroid - Relatively slow. Limited by:
- speed of gene transcription

Question 16

Receptors can be targets for drugs in either an agonistic or antagonistic fashion. What do these terms mean in this context and what are the 2 types of antagonism (hint = steric / function)

Answer 16

Agonist: Mimic the natural ligand for the receptor and thus activate it even in the absence of the natural signal

Antagonist: Block the action of the natural ligand inhibiting the action of the receptor

There are 2 types of antagonist:
- Direct antagonism: directly compete with ligand for binding
- Allosteric antagonism: Inhibit receptor function by binding at a different site

Question 17

Development of the kidney involves a variety of signalling molecules relaying information between the ureteric bud and the metanephrogenic mesenchyme. What are some signals and their function in ureteic branching

Answer 17

TGFb + BMP4: Elongation
BMP7: Go Straight
BMP2: Keep Out
GDNF: Branch

Question 18

Define ‘weak emergence’

Answer 18

Weak emergence is essentially the overall effect of a combination of different interactions in a biological system. An example is kidney development that utilises a variety of different signals and receptors to stimulate growth.

Question 19

Match the stage of kidney development to what’s happening:

a) Specification of the intermediate mesoderm into the nephrogenic mesoderm
b) Nephron mesoderm divides into nephron progenitor cells
c) Simultaneous with b), the UB grows and branches
d) UB induces nephron progenitors to differentiate into specific cell types
e) Forms the distinct structures of the kidney such as glomerulus and renal tube
f) Development of blood vessels

• Nephron maturation
• Vascularisation
• Kidney specification
• Ureteric bud formation
• Nephron formation
• Reciprocal induction

Answer 19

a) Kidney specification
b) Nephron formation
c) UB formation
d) Reciprocal induction
e) Nephron maturation
f) Vascularisation

Question 20

What is the definition of a drug?

Answer 20

a chemical that produces a biological effect when given to a living organism

Question 21

What additional criteria do the FDA outline when considering drugs

Answer 21

• its structure must be known
• a drug is not a nutrient or essential dietary requirement

This separates drugs from medicines

Question 22

The advent of DNA technology has led to the introduction of many drugs that are broadly named biopharmaceuticals. What 3 biological mechanisms do these include?

Answer 22

• Enzymes and blood components
• Hormones
• Humanised monoclonal antibodies (Mab)

Question 23

What 2 major principles govern the therapeutic use of drugs against disease

Answer 23

• Selectivity: selective action on the target tissue
• Specificity: this interaction between drug and target should be unique/specific (usually unmet = side effects)

Question 24

What is the definition of a receptor in the context of drug administration

Answer 24

any target molecule with which a drug has to combine in order to elicit its desired effect

Question 25

What are the 4 recognised drug targets

Answer 25

• Receptors
• Ion channels
• Enzymes
• Transporters (carrier molecules)

Question 26

The AFFINITY of a drug to bind to its target can be quantified in terms of an equilibrium constant: Ka from the Hill Langmuir equation:

[AR]/[RT] = [A]/Ka // [A]/Ka +1

What does each symbol stand for

Answer 26

[AR] = drug receptor complex concentration
[RT] = total number of receptors concentration
[A] = concentration of drug
Ka= Equilibrium constant (mol/l) for drug A binding to R

Question 27

In the context of drugs, what is the equilibrium constant

Answer 27

The concentration of a drug which occupies 50% of the available receptors. The smaller its value, the higher the affinity of the drug.

Question 28

What is the definition of efficacy

Answer 28

the ability of an agonist, once bound to the target, to elicit an effect

Question 29

What is the difference between FULL agonists and PARTIAL agonists

Answer 29

full: elicit the maximum response from a tissue
partial: cannot elicit the maximum response no matter how much drug is applied

Question 30

What is the definition of an antagonist in relation to efficacy and affinity

Answer 30

Drugs that bind with high specificity to a receptor but do not produce a response. They possess affinity but no efficacy

Question 31

Give the definition of:
a) Competitive reversible antagonism
b) Competitive irreversible antagonism
c) Allosteric modulators

Answer 31

a) Bind reversibly to the same site as the agonist
b) Same but bind irreversibly
c) Drugs that bind to a site distinct from the agonist binding site of a receptor but modulate the agonist response (can +ively or -ively affet response)