G-protein linked receptors Flashcards
What are G-protein linked receptors?
7 pass transmembrane receptors
Which side of the G-protein coupled receptor is the hormone binding site?
Extracellular
Which side of the G-protein receptor binds the G protein?
INtracellular
What does activation of the G-protein cause?
GDP is exchanged for GTP
GTP causes beta-gamma subunit to dissociate
Which subunit (alpha) (betagamma) of the G-protein is the most active?
Alpha
Does the betagamma unit have signaling properties?
Yes
How is GTP hydrolyzed after it is bound to the G-protein?
Alpha unit has GTPase activity
What is the messenger protein for Gs? What in the function of Gs?
increases cAMP
Gs increases protein kinase A activity
What is the messenger for Gi? What is the function of Gi?
Decrease cAMP
decreases protein kinase A activity
What are the 2 messenger proteins for Gq? What is the function for each?
IP3/DAG - protein kinase C
NO/cGMP - protein kinase G
What G protein is associated with the cardiac pacemaker (sinus node)?
Gs & cAMP pathway
What is the ‘funny current’?
If: spontaneous current that causes action potential in heart
What is the Ica,l current?
Calcium current activates at threshold of funny current and generates AP
What type of receptor is the cardiac pacemaker pathway?
Beta-adrenergic
Release of norepinephrine will have what activity on heart rate?
Increased stimulation of If and Ica,l currents
Describe pathway of epinephrine binding to a G-protein coupled receptor
NE binds to Beta-adrenergic receptor Gs protein is activated Adenylyl cyclase binds alpha-s subunit cAMP is produced cAMP activates Na+ channels (If) cAMP activates protein kinase A Protein kinase A activates Ca+ channel (Ica,l)
What causes cAMP to be down regulated and the channels to close?
Ne leaves Beta-adrenergic receptor
Gs protein self-hydrolyzes GTP to GDP
Betagamma subunit associates again
Phosphodiesterase breaks down cAMP
Na+ channel is closed
Phosphatase takes phosphate off of Ca+ channels
What effect does Acetylcholine have on heart rate?
Gi protein inhibits If (funny current) and Ica,l (action potential)
Describe pathway of acetylcholine binding to G-protein receptor
ACh binds to M2 muscarinic receptor
GTP replaces GDP and betagamma unit dissociates
Adenylyl cyclase binds to alpha-i subunit
cAMP is downregulated
Na+ channels do not open (If)
Lack of protein kinase A to phosphorylate Ca+ channels
Describe pathway of epinephrine binding to G-protein receptor in vascular smooth muscle to cause contraction
NE binds to alpha-1 adrenergic receptor
Phospholipase C binds to alpha-q subunit
PIP2 associates with Phospholipase C to produce DAG & IP3
IP3 opens Ca+ channels
Ca+ binds to Calmodulin-myosin light chain kinase complex
DAG activates protein kinase C
Protein kinase C phosphorylates CPI-17
CPI-17 inhibits myosin light chain phosphatase so phosphorylated myosin retains affinity for actin binding site
How is Gq in smooth muscle down-regulated to cause relaxation?
NE leaves Gq receptor
alpha-q subunit hydrolyzes GTP to GDP
IP3 and DAG are broken down
Phosphatases dephosphorylate CPI-17 which upregulates myosin light chain phosphatase
MLCP dephosphorylates MLC which decreases myosin’s affinity for actin
Describe the histamine G-protein pathway
Histamine binds to H1-histaminergic receptor
Phospholipase C binds to alpha-q subunit
PIP2 is broken to IP3 and DAG by phospholipase C
IP3 opens Ca+ channel
Ca+ binds to Nitric oxide synthase
NOS produces NO from arginine
NO stimulates guanylyl cyclase to produce cGMP from GTP
cGMP activates protein kinase G which phosphorylates myosin phosphatase target 1
MYPT-1 produces myosin phosphatase
What is the big difference between Gq/NO and Gq/NE
IP3 causes relaxation in Gq/NO
DAG does not activate protein kinase C in Gq/NO
so no CPI-17 during Gq/NO
Gq/NE causes contraction
Gq/NO causes vasodilation
How is histamine down-regluated?
Histamine leaves H1-histaminergic receptor
alpha-q subunit hydrolyzes GTP to GDP
IP3, DAG are broken down
NO breaks down
cGMP is broken down by phosphodiesterases
Phosphattases dephosphorylate Myosin phosphatase target 1
Name G-protein receptor & type and action for norepinephrine in the heart
Gs, B1-adrenergic, increase heart rate
Name G-protein receptor & typeand action for epinephrine in the arteries
Gs, B2-adrenergic, vasodilation
Name G-protein receptor & type and action for norepinephrine in the bronchi
Gs, B2-adrenergic, bronchiodilation
Name G-protein receptor & type and action for epinephrine in the muscle
Gs, B2-adrenergic, glycogen breakdown
Name G-protein receptor & type and action for vasopressin in the kidney
Gs, V2, water reabsorption
Name G-protein receptor & type and action for histamine in the stomach
Gs, H2, Acid secretion
Name G-protein receptor & type and action for glucagon in the liver
Gs, G, glycogen breakdown
Name G-protein receptor & type and action for ACTH in the adrenal cortex
Gs, ACTH-Receptor, Cortisol secretion
Name G-protein receptor & type and action for Thyroid stimulating hormone in the heart
Gs, TSH-Receptor, thyroid hormone synthesis & secretion
Name G-protein receptor & type and action for acetylcholine in the heart
Gi, M2, decreased heart rate
Name G-protein receptor & type and action for adrenaline in the neuron
Gi, A2-adrenergic, decrease transmitter release
Name G-protein receptor & type and action for norepinephrine in the arteries (Gq/IP3)
Gq-IP3, A1-adrenergic, vasoconstriction
Name G-protein receptor & type and action for acetylcholine in the bronchi (Gq-IP3)
Gq-IP3, M1, M3, contraction
Name G-protein receptor & type and action for acetylcholine in the pancreas
Gq-IP3, M1, M3, stimulate insulin secretion
Name G-protein receptor & type and action for Angiotensin in the arteries
Gq-IP3, AT1, AT2, Vasoconstriction
Name G-protein receptor & type and action for vasopressin in the arteries
Gq-IP3, V1, Vasoconstriction
Name G-protein receptor & type and action for acetylcholine in the vascular wall epithelium
Gq-NO, M3, vasodilation
Name G-protein receptor & type and action for histamine in the vascular wall epithelium
Gq-NO, H1, Vasodilation
