Cell Communication

Question 1

How can signals cross membranes?

Answer 1

• Exocytosis (constitutive or evoked)
• Channels and transporters (passive or gated)
• Free diffusion (steroids/gasses)

Question 2

What is paracrine signaling?

Answer 2

Local signalling btw cells

Question 3

What is synaptic signaling?

Answer 3

Electrochemical signalling btw neurons
Signal is rapidly and SPECIFICALLY transmitted

Question 4

What is endocrine signaling?

Answer 4

Long range, slow signalling via hormones that have high affinity receptors

Question 5

What is gaseous signaling?

Answer 5

Gasses diffuse through plasma membrane to intracellular receptors

Question 6

What are ionotrophic receptors?

Answer 6

Selective ligand-gated membrane channel that lets ions flow down their gradient
Excitatory: allows Na+ through
Inhibitory: allows Cl- through

Question 7

What are metabotrophic receptors?

Answer 7

G-protein coupled receptors
Terminated by hydrolysis of GTP to GDP

7 trransmembrane structure

Question 8

What are kinase receptors?

Answer 8

They phosphorylate themselves when activated, creating sites for other molecules to bind and become phosphorylated
Terminated by phosphotases

Question 9

What are steroid receptors?

Answer 9

Small hydrophobic molecules activate these receptors, which are usually intracellular and then usually go on to regulate gene transcription

Question 10

List the four different receptors in order from fastest to slowest and what their limitations are

Answer 10

1. Ionotrophic: limited by size of receptor pore and diffusion gradient
2. Metabotrophic: limited by # of enzymatic reactions
3. Kinase: limited by # of enzymatic reactions
4. Steroid: limited by speed of gene transcription

Ionotrophic= v fast
Metabotrophic= medium fast
Kinase= medium fast
Steroid= slow

Question 11

How can the same signal can have multiple outcomes depending on the receptor? Examples?

Answer 11

Some receptors have different affinites/efficacies so even in the same location the outcome would depend on signal concentration

Question 12

What drugs target cell signalling receptors?

Answer 12

Agonists: mimic natural ligand (stimulate receptor)
Antagonists: block natural ligand (block receptor)

Question 13

Whats the difference between direct antagonism and allosteric antagonism?

Answer 13

Direct= directly competing with ligand for binding
Allosteric= Inhibit receptor by binding at a separate site

Question 14

What does weak emergence mean?

Answer 14

the presence of properties at system level that are not present at component level

Question 15

What evidence suggests that renal development is regulative and not following an inflexible genetic blueprint?

Answer 15

Hypothesis: cells surrounding UB secrete something that controlls UB branching
Test hypothesis: test if proteins are signaling UB branching by A. interrupt signal, B. give fake signal
A. Interrupted signal with anti-GDNF= unusually long branches showed growth and branching are seperate
B. Making own message: GDNF, HGF, and TGF-B only GDNF triggered branching

UB= uteric bud

Question 16

What is a drug?

Answer 16

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

Question 17

Where do drugs come from?

Answer 17

Plants (opiods), fungi (penicillian), microorganisms (Rapamycin), synthetic chemicals (benzos), animals (insulin)

Question 18

Why is specificity so important in drug action?

Answer 18

Because dont want drug acting on other things and fucking everything else up

Question 19

What are biologics/biopharmaceuticals?

Answer 19

Wide range of medicinal products such as vaccines,
antibodies and hormones created by biological processes
Examples:
1. Enzymes and blood components. e.g. urokinase “clot buster”, Factor VIII (for Haemophilia)
2. Hormones. e.g. insulin, growth hormone, erythropoietin, interferon
3. Humanised monoclonal antibodies (Mab). e.g. Trastuzumab (Herceptin) used to block the HER2/neu receptor in breast cancer. Infliximab – Mab against TNF, and used to treat rheumatoid disease, Chrohn’s disease.

Question 20

State the four different drug targets:

Answer 20

1. Ligand gated ion channels
2. G-protein coupled receptor
3. Catalytic receptor
4. Nuclear receptors

Can be Receptors, Ion channels, Enzymes, Transporters (carrier molecules

These molecular targets may be found;
- anchored in the cell membrane
- outside cells- in the extracellular space
- inside cells - in the cytoplasm, in intracellular membranes, or in the nucleus

Question 21

What is affinity? How is it quantified?

Answer 21

• the ability of a drug to bind to its drug target
• Quantified as KA = equilibrium constant (mol/l) for drug A binding to R in the Hill-Langmuir equation

Question 22

What is efficacy?

Answer 22

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

Question 23

Whats the difference between full agonists and partial agonists?

Answer 23

Full agonists can elicit max response of a tissue, while partial agonists cannot no matter how much is given. Shows the difference between affinity and efficacy

Both bind to the receptors aka affinity, and at appropriate concentrations occupy all receptors. Thus, binding is not sufficient to elicit a response.

Question 24

If the affinity of a lignad is high, is the equilibrium constant high or low?

Answer 24

The KA would be very large, and KD be very small.
- KA is the ligand concentration at which 50% of receptors are occupied
- High affinity = small amt of drug needed to occupy 50% of receptors
- A drug with a KD = 1x10-9M has higher affinity than one with a KD = 1x10-6M

Question 25

Do antagonists have efficacy?

Answer 25

They have affinity but no efficacy because they do not stimulate receptorr

Question 26

What are competitive reversible antagonists?

Answer 26

Compete with agonists for their receptors, but if you inc agonist conc you can restore agonist occupancy

Question 27

What are competitive irreversible antagonists?

Answer 27

Antagonist does not dissociate from the receptor, no matter how much agonist is added it will not reverse the effect of the antagonist

Question 28

What are allosteric modulators?

Answer 28

• drugs that bind to a site distinct from the agonist binding site of a receptor but modulate the agonist response.
• They can be positive (increase the effect of the agonist), negative (decrease agonist effect) or neutral (no effect on agonist response).

Question 29

Give examples of non-conventional medicines

Answer 29

Enzymes: streptokinase, a bacterial enzyme that can liquefy blood clots by converting plasminogen to plasmin, used following myocardial infarction
Medicines that react chemically with small molecules: e.g. Al(OH) to neutralise gastric acidity.
Nutrients: e.g. vitamins, minerals, lipids, carbohydrates, amino acids