Topic 3 - Mechanisms of Hormone Action -- Surface Receptors Flashcards
What does the rate of association equal?
Rate of dissociation
[H]
Concentration of free hormone
[R]
Concentration of receptor
[HR]
Concentration of hormone-receptor complex or bound hormone
Kd
Equilibrium dissociation constant (defines affinity)
–> concentration of free H when 50% R are bound
What does the receptor tell you?
How sensitive the hormone was
What gets tagged with fluorescent?
The hormone
How do you find the receptors?
Use antibodies with fluorescent tags
What does Kd tell us?
Tells us how sensitive or how many receptors there are of the binding constant of the receptor to its hormone
What is the common form of most receptors?
Open and not bound (until more substrate is added)
What happens to the affinity when you have a low [H]?
You get a higher affinity
What happens to the [H] when you have a low affinity?
High [H]
Where would you find Ro on a graph?
X-intercept
What is the formula for slope on a scatchard plot
- 1/Kd
What are the axis labels on a scatchard plot?
y = [HR]/[H] x = [HR]
ICYP
Iodocyanopindolo
What is a pindolol?
Nonselective beta blocker
What is ICYP, and what is its derivative used for?
It is a Beta1 receptor antagonist and its derivative is used in mapping the distribution of beta adrenoreceptors in the body
Where is ICYP produced?
In the adrenal medulla
What are the 5 main types of cell surface receptors?
- 7 transmembrane domain
- GPCR
- AC
- PLC - Growth factor receptor
- tyrosine kinase domain attached - Cytokine receptors
- tyrosine kinase separate - Guanylyl cyclase receptors
- cyclase attached - Novel cell surface receptors
- ferroportin
AC
Adenylyl cyclase
PLC
Phospholipase C
G-protein receptor disease
Mutations in G protein receptors important pathology in endocrine disorders; often need homozygous mutation to have loss of function since excess receptors; also could have gain of function, if mutation causes constitutive activation; a single point mutation may also alter binding specificity or receptor desensitization
GTP
Guanosine triphosphate
GDP
Guanosine diphosphate + free phosphate (Pi)
What are the 3 heterodimer subunits?
- Alpha
- Beta
- Gamma
Alpha s
Stimulation of adenylyl cyclase
Alpha i
Inhibition of adenylyl cyclase
Alpha q/11
Stimulation of PLC
What kind of energy activity does Alpha have?
GTPase activity
GTP bound = active
GDP bound = inactive
What do beta and gamma subunits act as?
Dimers
What are G proteins made up of? (3)
Alpha, beta and gamma subunits
G protein signalling general mechanisms (8)
- Inactive complex
- Ligand binds creating a conformation change in receptor
- Receptor g-protein complex forms and GDP dissociates from alpha
- GTP binds
- G alpha -GTP dissociates from receptor and beta/gamma subunits
6a. G alpha-GTP acts on the effectors (eg. PLC, AC)
6b. beta/gamma can also act on effectors - Intrinsic GTPase of alpha converts GTP to GDP
- Subunits re-associate (repeat)
What does alpha s effect? (3)
- Adenylyl cyclase
- Ca channels
- K channels