Drug Action + Cell Signaling

Question 1

Targets of drug action

Answer 1

Receptors, ion channels, enzyme and carrier molecules (eg transporter proteins)

Question 1

Receptor - agonist direct changes

Answer 1

Opening/closing ion channels

Question 2

Agonist-receptor Transduction Mechanisms Changes

Answer 2

enzyme activation/inhibition, ion channel modulation and DNA transcription

Question 3

Antagonist-Receptor Changes

Answer 3

Nothing

Question 4

3 types of receptors

Answer 4

cell surface (gives fastest response), intracellular receptors and organelle/nuclear receptors (slowest response)

Question 5

Ion Channels Outline

Answer 5

Contain ligand binding sites. Ligands bind to either widen/narrow channels pores

Question 6

How drugs target enzymes

Answer 6

Substrate analogues, false substrates and prodrugs

Question 7

Substrate analogues Outline

Answer 7

Drugs bind to enzyme binding site preventing substrate from attaching

Question 8

False Substrates Outline

Answer 8

Drugs that are close enough in shape to substrate that enzyme does convert it to product. The product is atypical (doesn’t preform the same actions)

Question 9

Prodrug Outline

Answer 9

Prodrug (inactive) binds to enzyme receptor and leaves as an active drug species

Question 10

Carrier Molecules Antagonist Interaction Outline

Answer 10

Antagonists bind either competitively or non-competively to transport protein. Molecules are unable to pass through

Question 11

What is transported by transport proteins

Answer 11

Substances moving against their concentration gradient and hydrophilic molecules. Eg furosemide and hydrochoretizide block kidney to prevent Na+ kidney reabsorption

Question 12

4 receptor classes

Answer 12

ligand-gated (fastest), g-protein coupled, enzyme linked receptors and nuclear receptors (slower)

Question 13

Ligand gated ion channels Outline

Answer 13

Fastest (miliseconds). Especially ion gated

Question 14

G-protein coupled Receptors Outline

Answer 14

Fast (seconds). Important for ANS. Metabatronic

Question 15

Enzyme linked receptors Outline

Answer 15

Intermediately slow (hours) as it has multiple steps. Works by dimmerisation (bringing a receptor closer. undergoes phosphorylation in intracellular domain)

Question 16

Nuclear Receptors

Answer 16

Slowest (hours to days) (as furthest distance travelled). Very potent effects signaling in cell

Question 17

G-protein coupled receptors appearance Outline

Answer 17

Single polypeptide chain with 7 transmembrane loops (consisting of alpha helical regions). Extracellular regions = n-domains. intracellular regions = c-domains. Largest intracellular loop (c-domain) interacts with g-protein

Question 18

3 G-protein coupled receptors families

Answer 18

A (rhodopsin), B (secretin/glucagon, peptide receptors) and C (glutamate/gaba receptors). Sequence homology within families (not between). Families show differences in n-terminal length and location of binding site from each other

Question 19

3 subunits of g-protein receptors

Answer 19

Alpha (both anabolic and catalytic GTP), beta and gamma

Question 20

G Alpha (s) Function

Answer 20

Stimulates adenylyl cyclase (increase cAMP)

Question 21

G Alpha (i) Function

Answer 21

inhibits adenylyl cyclase (decrease cAMP)

Question 22

G Alpha (q) Function

Answer 22

Activates phospholipase C. Increases secondary messages production: inositol phosphate and diacylglycerol

Question 23

G Beta and Gama Function

Answer 23

Opens K+ channels, closes voltage gated Ca^2+ channels, activate GPCR kinases and activate mitogen-activated protein kinase cascade.

Question 24

Norepinephrine and b-adrenergic receptor (G Alpha (s)) progression

Answer 24

Increase adenylyl cyclase = increased cAMP = increased protein kinase A = increase protein phosphorylation

Question 25

Dopamine and Dopamine D2 receptors (G alpha (i)) progression

Answer 25

Decraesed adenylyl cyclase = decreased cAMP = decreased protein kinase A = decreased protein phosphorylation

Question 26

Glutamate and mGluR ( G alpha (q)) progression

Answer 26

Phospholipase C production = diglyecerol and IP3 production = protein kinase C production = Ca^2+ release = increased protein phosphorylation

Question 27

2 targets of g-proteins

Answer 27

adenylyl cyclase system and phospholipase C/IP3 system

Question 28

Function of kinases and their control

Answer 28

Proteins are activated or inactivated by phosphorylation

Question 29

Kinase Linked Receptors Appearance

Answer 29

Single chain, membrane spanning helical region. Large extracellular ligand binding domain. Intracellular domain varies in size and function

Question 30

Kinase Linked Receptors Function

Answer 30

cell differentiation, dividion and immune response

Question 31

3 classes of kinase receptors

Answer 31

Receptor tyrosine kinase, serinine/theronine kinase and cytosolic kinases (associate with cytokine reecptors with no intrinsic enzyme activity)

Question 32

Steps of cytokine pathway

Answer 32

agonist binding, dimerisation, phosphorylation and gene transcription

Question 33

Nuclear Receptors appearance

Answer 33

monomeric proteins, ligand activated transcription factors and located in cytosol or nucleus. Contains a DNA binding domain known as the hormone response element