GPCRs Flashcards
G-protein coupled receptors
*7-pass transmembrane domains
*integrate signals outside of the cell with signals inside the cell
general mechanism for GPCRs
*GPCR is normally bound to GDP
*when a ligand binds the GPCR, this promotes swapping out of GDP for GTP, causing the alpha subunit to diffuse away
*the alpha subunit has a GTPase activity, and thus can turn itself off (Galpha GTP = active; Galpha GDP = inactive)
what are the 4 types of the alpha subunit of the GPCR
1) Galpha S
2) Galpha I
3) Galpha Q
4) Galpha 12/13
Galpha S function
*stimulates cAMP production (adenylyl cyclase converts ATP into cAMP)
*cAMP activates PKA (protein kinase A)
Galpha I subunit function
*inhibits cAMP production (inhibits adenylyl cyclase from making cAMP)
Galpha Q subunit function
*activates phospholipase C (PLC)
*PLC cleaves PIP2, and IP3 diffuses away
*IP3 releases calcium from smooth ER
*calcium & diacylglycerol activate protein kinase C (PKC)
Galpha 12/13 subunit
promotes actin remodeling
what are the 3 ways that GPCR signaling must be turned off
1) turn off RECEPTOR
2) turn off Galpha subunit
3) turn off second messenger
how do we turn off the GPCR?
1) desensitization of GPCRs by phosphorylation (accomplished by GRK (G-protein couple receptor kinase))
2) arrestin binding
3) internalization of GPCR
4) once internalized, the ligand is removed and the receptor can be recycled or degraded
how can we turn off the second messenger?
NEGATIVE FEEDBACK:
-some second messengers stimulate molecules that REMOVE THEM (example: phosphodiesterase is activated by PKA and functions to cleave cAMP)
how can we turn off the Galpha subunit?
Galpha subunit has GTPase activity, and therefore turns itself off
*when GTP is bound, subunit is active
*when GDP is bound, subunit is inactive
cholinergic receptors
*2 types: nicotinic and muscarinic
*receive Ach
adrenergic receptors
*2 types: alpha and beta
*receive norepinephine
what amino acid is the precursor for norepinephrine
tyrosine
D1 receptors in the sympathetic nervous system
*D1 = dopamine receptor 1
*present on renal vasculature smooth muscle
*receives dopamine
alpha 1 receptor
*adrenergic receptor (receives norepinephrine)
*G alpha Q subunit
alpha 1 receptor - functions
VASOCONSTRICTION:
1) dilate pupils (mydriasis)
2) constricts blood vessels (increase blood pressure)
3) constrict sphincters
4) increase Na+ and water reabsorption in proximal convoluted tubules (PCT)
together, constriction of blood vessels & increased reabosorption contribute to increasing the blood pressure
alpha 2 receptor
*adrenergic receptor (receives norepinephrine)
*G alpha I subunit
alpha 2 receptor - functions
1) inhibit preganglionic sympathetic stimulation
2) inhibit secretion
beta 1 receptor
*adrenergic receptor (receives norepinephrine)
*G alpha S subunit
beta 1 receptor - functions
1) stimulate JGA renin release
2) INCREASE HR
beta 2 receptor
*adrenergic receptor (receives norepinephrine)
*G alpha S subunit
beta 2 receptor - functions
1) dilate bronchioles
2) INCREASE HR
3) inhibit GI peristalsis
4) ciliary muscles in eye
5) dilate skeletal muscle vasculature (send blood to skeletal muscle)
beta 3 receptor
*adrenergic receptor (receives norepinephrine)
*G alpha S subunit
beta 3 receptor - functions
1) increase lipolysis (energy from fat)
2) INHIBIT BLADDER WALLS (stops you from peeing)
what receptor is found on sweat glands
M3 (receives Ach but acts as a part of sympathetic response)
M1 receptor
*cholinergic receptor (receives Ach)
*G alpha Q subunit
M1 receptor - functions
1) higher cognitive functions
2) stimulates enteric nervous system
M2 receptor
*cholinergic receptor (receives Ach)
*G alpha I subunit
M2 receptor - functions
*SLOWS heart rate
M3 receptor
*cholinergic receptor (receives Ach)
*G alpha Q subunit
M3 receptor - functions
1) close pupil (myosis) & accommodate the lens
2) constrict bronchioles
3) increase secretions
4) relax sphincters
5) increase peristalsis
*basically, M3 is all of the parasympathetic fxns except HR
metabotropic receptors
*ligand binding alters second messenger, causing a variety of effects
*examples include muscarinic and adrenergic receptors
ionotropic receptors
*ligand binding changes conductance (allows ions to flow in/out by opening an ion channel)
*example is nicotinic acetylcholine receptors
olfaction - pathway, receptor and channel
*subunit = G alpha S
*odorant molecule binds to an odorant receptor (GPCR)
*cAMP produced activates a CNG channel (cyclic nucleotide-gated channel)
*opening the CNG channel allows influx of Na+ and Ca2+ into the cell
phototransduction - pathway, receptor, and channel
*opsins are GPCRs with G alpha T subunit (t = transducin)
*a photon strikes the GPCR, activating it
*G alpha T dissociates from the rest of the receptor and interacts with its effector, a phosphodiesterase (PDE)
*PDE converts cGMP to GMP
*less cGMP closes ion channels, leading to HYPERPOLARIZATION
gustation: detection of salty and sour
*direct inflow of cations (either Na+ or H+), depolarizing the cell and releasing the neurotransmission
gustation: detection of sweet, bitter, and umami
*GPCRs with G alpha Q subunit
