Flashcards in Basics Deck (23):
Therapeutic Index =
Maximum non-toxic dose . minimum effective dose /
Statements can only be falsifiable
No experiment is ever useless
4 types of receptors:
LGIC, GPCR, Kinase-linked + related & I.C./ nuclear related receptors
An example of a pentamer, tetramer and trimer LGIC
Cys-loop family, glutamate, P2X
3rd I.C. loop of GPCR's is critical for
Interaction with I.C. G-proteins
Domains of Kinase-linked receptors
Extracellular ligand-binding and intracellular effector
Common mech of action for kinase-linked receptors
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
Intracellular/ nuclear receptors are different from other receptors, how?
Soluble monomeric proteins that regulate gene transcription through dimeric form from ligand binding
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
LGIC time frame
~ 1 ms
Difference between glutamate LGIC and GABA/ glycine?
Cation v anionic chloride channels
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.
Functions of Gs
activates adenylyl cyclase and Ca2+ channels
Functions of Golf
activates adenylyl cyclase in olfactory sensory neurons
inhibitis acdenylyl cyclase and activates K+ channels
Activates K+ cnhannels
inactivates Ca2+ channels
activates cGMP phosphodiesterase in vertebrate rod photoreceptors
What does PLC do?
Splits membrane phospholipid phosphatidylinositol biphosphate to InsP3 and DAG
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