Pharmacodynamics III

Question 1

Describe first messengers

Answer 1

Extracellular substances that include peptide hormones: Epinephrine, growth factors, NTs
Usually hydrophillic molecules, first messengers may not physically cross bilayer to initiate changes within cell directly

Question 2

Describe how an extracellular signal can be propagated intra-cellularly

Answer 2

Cells have signal transduction mechanisms to transduce first into second messengers

Question 3

Describe the link between first and second messengers

Answer 3

Second messengers are coupled downstream to multi-cyclic kinase cascades to greatly amplify the strength of the original first messenger signal

Question 4

Describe second messengers

Answer 4

Intracellular signalling molecules released by cell to trigger physiological changes eg proliferation, differentiation, migration, survival, apoptosis
Initiate signal transduction cascades

Question 5

Name examples of signal transduction cascades

Answer 5

cAMP, cGMP, IP3, DAG, Ca

Question 6

Name receptors and signal mechanisms

Answer 6

G-proteins/second messengers, Ligand-gated ion channels, Tyrosine kinase receptors, intracellular receptors

Question 7

Describe G-protein coupled receptors

Answer 7

7 transmembrane, metabotropic, many hormones, slow transmitters > Eg muscarinic ACh receptors

Question 8

Describe different types of second messengers

Answer 8

Adenylyl cyclase
Phospholipase C (PLC)
Ion channels
RhoA/Rho kinase

Question 9

Describe Adenylyl cyclase

Answer 9

Enzyme responsible for cAMP formation

Question 10

Describe Phospholipase C

Answer 10

Enzyme that catalyses hydrolysis of PIP2 into inositol triphosphate and DAG

Question 11

Describe RhoA/Rho kinase

Answer 11

System that controls activity of many signalling pathways, controlling cell growth, proliferation, smooth muscle contraction

Question 12

Describe GPCR adrenoceptors

Answer 12

2 groups: a/b
a receptor causes contraction
b linked to adenylate cyclase, agonist binding so causes rise in intracellular concentration of second messenger cAMP

Question 13

Describe ligand gated ion channels

Answer 13

Mediate fast synaptic events on nerves/muscles, ms responses, eg ACh nicotinic receptors

Question 14

Describe the structure of ligand gated ion channels

Answer 14

a2, b, y, s subunits
2 ACh bind
One helices (M2) from each subunits used for channel
Small change in M2 determines ion selectivity

Question 15

Describe the action of ligand gated ion channels

Answer 15

Nicotinic receptor linked ion channel conduct Na+ in/K+ out of cells causing depol
Open channel conducts 10^7 ions/sec (norm - 1-2ms)
Different agonist have different closing rates

Question 16

What are tyrosine kinase receptors?

Answer 16

Enzymes that transfer phosphate group from ATP to protein

Question 17

Describe tyrosine kinase receptors

Answer 17

Receptors from hormones (Insulin)/Growth factors, involves dimerisation causing autophosphorylation of tyrosine residues, activates many acceptor proteins

Question 18

Name different types of tyrosine kinase receptors and what they’re used for

Answer 18

Toll-like receptors - Innate immunity
Growth factors - Epidermal GF
Insulin receptor

Question 19

What are the 2 important signalling transduction pathways?

Answer 19

Ras/Raf/MAP - Vital in cell division, growth, differentiation
Jak/Stat pathway - Control synthesis/release of inflammatory mediators

Question 20

Describe intracellular receptors

Answer 20

Receptors inside cell, ligand enters cell, changes protein synthesis so slow effects, all have DNA binding domain

Question 21

Describe the uses of intracellular receptors

Answer 21

For steroid hormones (T4)
Promote/Suppress gene expression
Regulate lipid metabolism