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Flashcards in Basics Deck (23):
1

Therapeutic Index =

Maximum non-toxic dose . minimum effective dose /
TD50/ ED50

2

Popper's law

Statements can only be falsifiable

3

Carson's consolation

No experiment is ever useless

4

4 types of receptors:

LGIC, GPCR, Kinase-linked + related & I.C./ nuclear related receptors

5

An example of a pentamer, tetramer and trimer LGIC

Cys-loop family, glutamate, P2X

6

3rd I.C. loop of GPCR's is critical for

Interaction with I.C. G-proteins

7

Domains of Kinase-linked receptors

Extracellular ligand-binding and intracellular effector

8

Common mech of action for kinase-linked receptors

Dimerisation

9

Outline tyrosine kinase receptor activity

Auto-phosphorylation of tyrosine residues on each cytoplasmic domain -> act as binding sites -> leads to binding of intracellular proteins (SH2 domain proteins) -> become phosphorylated and activated

10

Intracellular/ nuclear receptors are different from other receptors, how?

Soluble monomeric proteins that regulate gene transcription through dimeric form from ligand binding

11

Example of LGIC and mech of action

nAChR - ACh binds leading to conformational change so Na+/K+ ions flow in or out - coupling between receptor activation and response

12

LGIC time frame

~ 1 ms

13

Difference between glutamate LGIC and GABA/ glycine?

Cation v anionic chloride channels

14

Outline GPCR activation using Gs

(1) At rest the  subunit of the Gs-protein binds GDP
(2) When the receptor is activated, its affinity for Gs increases and
(3) it interacts with the Gs-protein. The  subunit catalyzes the exchange of GDP for GTP.
(4). The GTP-bound G-protein acts as the first messenger and interacts with an effeczor molecule
(e.g., an enzyme, in this case adenylate cyclase, or an ion channel etc.).
(5) The enzyme becomes activated producing cAMP. The G-protein also has GTPase enzymatic
activity, hydrolyzing GTP to GDP. (6). The GDP stays bound to the G protein, so the G protein
reverts to the resting state, stage (1). This switches off the G protein’s action.

15

Functions of Gs

activates adenylyl cyclase and Ca2+ channels

16

Functions of Golf

activates adenylyl cyclase in olfactory sensory neurons

17

Gi

inhibitis acdenylyl cyclase and activates K+ channels

18

Go functions

Activates K+ cnhannels
inactivates Ca2+ channels
activates PLC-beta

19

Gt functions

activates cGMP phosphodiesterase in vertebrate rod photoreceptors

20

Gq functions

activates PLC-beta

21

What does PLC do?

Splits membrane phospholipid phosphatidylinositol biphosphate to InsP3 and DAG

22

Outline insulin receptor function

Binding of insulin -> autophosphorylation of catalytic domains -> phosphorylates insulin receptor substrate - 1 (IRS-1) -> high affinity binding site for docking and activation of other signalling molecules and proteins

23

Two stages of nuclease receptor response

1. direct induction of a few genes (30-60 mins)
2. late/ delayed response -> induction of secondary regulatory gene