Intercellular signalling pathways (2) Flashcards
Give examples of proteins involved in the GPCR pathway
- Adenylyl cyclase
- Phospholipase C
- PI3K
- cGMP Phosphodiesterase
- VOCCs
- GIRKs
- Ion Channels
What is the function of Adenylyl Cyclase?
Converts ATP to cAMP which will bind to PKA
Give examples of GPCRs that stimulates adenylyl cyclase
- Gs - coupled receptors
- B-adrenoreceptors
- D1-dopamine receptors
- H2-histamine receptors
Give examples of GPCRs that inhibit Adenylyl cyclase
- Gi coupled receptors
- alpha2-adrenoreceptors
- D2-dopamine receptors
- mu-opiod receptors
What does the R and C resemble on PKA
R : regulatory
C : catalytic
Describe the characteristics of PKA
- contains 2 catalytic and 2 regulatory units
- cAMP binding spot on regulatory units
State the function of cAMP
- Binds to regulatory units of PKA
- PKA undergoes confirmational change
- Catalytic subunits liberated and active
State the function of PKA
Phosphorylates proteins and enzymes in cytoplasm
State the function of Phospholipase C
PLC catalyses cleavage of PIP2 into IP3 and DAG
Is DAG an intrinsic protein?
Yes
State the fucntion of IP3 un relation to [Ca2+]
- Binds to IP3 receptor on ER which causes Calcium to be released from ER lumen into cytoplasm
- Increases cytoplasmic Ca2+ con by 5-10 folds
- [IP3] in cell can be rapidly increased by Gq proteins and growth factors
Give examples of GPCRs that stimulate PLC
- Gq-coupled receptors
- alpha1-adremoreceptors
- M1-muscuranic receptors
- H1-histamine receptors
What does GPCR pathway give rise to?
Signap Amplification
Give an example of clinical scenario where adrenaline/noradrenaline acts on B1-adrenoreceptors and effects Adenylyl cyclase
Inotropy in the heart
Describe the signalling pathway that causes Inotropy in the heart
- Adrenaline/noradrenaline binds to B1-adrenoreceptors
- Adenylyl cyclase stimulated - ATP to cAMP
- cAMP activates PKA
- PKA binds and activates VOCC
- VOCC open, Ca2+ diffuse into cytoplasm
- Increase [Ca2+], Increase force of heart contraction
Give examples of hormones and receptors that causes smooth muscle contraction
- Noradrenaline/adrenaline - alpha1-adrenoreceptors on vascular smooth muscle - vasoconstriction
- acetylcholine - M3-muscarinic receptors on bronchiolar smooth muscle - bronchoconstriction
- All muscle contraction utilise Gq - PLC - IP3/Ca2+, DAG/PKC pathways
What type of GPCR modulates neurotransmitter release?
presynaptic GPCR
Give an example of presynaptic GPCR and a ligand. Describe their pathway.
- mu-opiod receptor, morphine
- morphine binds to mu-opioid receptors
- yB subunit dissociates from g protein and binds to VOCC
- yB inhibits VOCC
- Ca2+ unable to diffuse into cytoplasm
What is the effect of inhibition of VOCC by yB subunit?
- Reduces Ca2+ influx
- reduces neurotransmitter release
State the characteristics of signal transduction in biological membranes
- Diverse : diverse range of stimuli, receptors and Gproteins
- Specific : specific ligand-receptor interactions
- Amplification : Allow small changes in extracellular signals to elicit significant changes in cellular behavior
