Cell Communication Flashcards
How can signals cross membranes?
- Exocytosis (constitutive or evoked)
- Channels and transporters (passive or gated)
- Free diffusion (steroids/gasses)
What is paracrine signaling?
Local signalling btw cells
What is synaptic signaling?
Electrochemical signalling btw neurons
Signal is rapidly and SPECIFICALLY transmitted
What is endocrine signaling?
Long range, slow signalling via hormones that have high affinity receptors
What is gaseous signaling?
Gasses diffuse through plasma membrane to intracellular receptors
What are ionotrophic receptors?
Selective ligand-gated membrane channel that lets ions flow down their gradient
Excitatory: allows Na+ through
Inhibitory: allows Cl- through
What are metabotrophic receptors?
G-protein coupled receptors
Terminated by hydrolysis of GTP to GDP
7 trransmembrane structure
What are kinase receptors?
They phosphorylate themselves when activated, creating sites for other molecules to bind and become phosphorylated
Terminated by phosphotases
What are steroid receptors?
Small hydrophobic molecules activate these receptors, which are usually intracellular and then usually go on to regulate gene transcription
List the four different receptors in order from fastest to slowest and what their limitations are
- Ionotrophic: limited by size of receptor pore and diffusion gradient
- Metabotrophic: limited by # of enzymatic reactions
- Kinase: limited by # of enzymatic reactions
- Steroid: limited by speed of gene transcription
Ionotrophic= v fast
Metabotrophic= medium fast
Kinase= medium fast
Steroid= slow
How can the same signal can have multiple outcomes depending on the receptor? Examples?
Some receptors have different affinites/efficacies so even in the same location the outcome would depend on signal concentration
What drugs target cell signalling receptors?
Agonists: mimic natural ligand (stimulate receptor)
Antagonists: block natural ligand (block receptor)
Whats the difference between direct antagonism and allosteric antagonism?
Direct= directly competing with ligand for binding
Allosteric= Inhibit receptor by binding at a separate site
What does weak emergence mean?
the presence of properties at system level that are not present at component level
What evidence suggests that renal development is regulative and not following an inflexible genetic blueprint?
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
What is a drug?
A chemical that produces a biological effect when given to a living organism
Where do drugs come from?
Plants (opiods), fungi (penicillian), microorganisms (Rapamycin), synthetic chemicals (benzos), animals (insulin)
Why is specificity so important in drug action?
Because dont want drug acting on other things and fucking everything else up
What are biologics/biopharmaceuticals?
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.
State the four different drug targets:
- Ligand gated ion channels
- G-protein coupled receptor
- Catalytic receptor
- 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
What is affinity? How is it quantified?
- 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
What is efficacy?
- the ability of an agonist, once bound to the target, to elicit an effect.
Whats the difference between full agonists and partial agonists?
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.
If the affinity of a lignad is high, is the equilibrium constant high or low?
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
