signalling pathways

cyclic AMP involves which G proteins

Gs and Gi

which pair of second messengers are produced by receptors coupled to Gq G proteins

IP3 and calcium

how is cAMP produced

• ATP → cAMP

• adenylyl cyclase as enzyme

• PPi produced as byproduct

phosphodiesterases

break down cAMP

direct actions of cAMP

• acts directly on HCN channels in the heart

• important in cardiac pacemaker cells in SA node

function of protein kinase A

• phosphorylates proteins

• phosphorylates Ser and Thr which changes target protein activity

inactive form of PKA

• 2 regulatory units

• 2 catalytic

how is PKA activated

• 2 cAMP binds to each regulatory subunit of PKA

• 4 cAMP mol in total

signaling via Gs

• agonist binds to receptor to activate

• GPCR interacts with Gs

• GDP → GTP replacement

• Gs splits into subunits alpha and gamma beta complex

• alpha s interacts with adenylyl cyclase

• increase production of cAMP

• alpha subunit hydrolyses GTP

• agonist leaves receptor

• inactivated

does Gs activate or inhibit adenylyl cyclase

• activates

• alpha s interacts with adenylyl cyclase

receptors coupled to Gs

• beta adrenergic receptors

• Adrenocorticotropic hormone receptors ACTH

• corticotropin-releasing hormone receptors

• adenosine receptors

adrenocorticotropic hormone receptor (ACTH)

• Gs coupled

• regulates cortisol production in adrenal glands

corticotropin releasing hormone

• Gs coupled

• when activated released ACTH adrenocorticotropic hormone

adenosine a2a receptor

• Gs

• inhibition of inflammation

beta adrenoreceptors

• both coupled to Gs

• beta 1 adrenoreceptor - inc heart rate and force of contraction

• beta 2 adrenoreceptor - inc vasodilation in smooth muscle

signaling via Gi

• agonist binds to GPCR

• Gi with alpha i

• GDP → GTP replacement

• alpha i with GDP inhibits adenylyl cyclase

• less cAMP produced

• hydrolyse GTP

• reassociate subunits of g protein

• agonist leaves receptor

• cAMP levels will raise again

does Gi inhibit or activate adenylyl cyclase

inhibit

what causes cAMP levels to rise again with Gi

• when the GTP hydrolysed

• G protein subunits reassociate

• Agonist leaves receptor

receptors coupled to Gi

• muscarinic acetylcholine receptors M2 and M4

• alpha 2 adrenergic receptors

• adenosine A1 and A3 receptors

PLC - phospholipase C interacts with which G protein

Gq

signaling via Gq qith PLC

• agonist activates receptor

• interacts with Gq protein

• GTP → GDP replacement

• alpha q disassociated and interacts with PLC

• acts on membrane lipid PIP2

• PLC cuts PIP2 → IP3 + DAG

• DAG remains

• IP3 released into cytoplasm

what does phospholipase c ( PLC ) cut membrane lipid PIP2 into

IP3 and DAG

function of IP3

• acts on IP3 receptor in ER

• IP3 receptor is calcium channel so calcium released

• calcium binds to ryanodine receptor

• activates another calcium channel

how many calcium ions bind to ryanodine receptor

4 calcium ions

function of protein kinase C

phosphorylates proteins

what is protein kinase c activated by

DAG and calcium

receptors linked to Gq

• M1, M3, M5 muscarinic acetylcholine receptors

• alpha1 adrenergic receptors