GPCRs

Question 1

G-protein coupled receptors

Answer 1

*7-pass transmembrane domains
*integrate signals outside of the cell with signals inside the cell

Question 2

general mechanism for GPCRs

Answer 2

*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)

Question 3

what are the 4 types of the alpha subunit of the GPCR

Answer 3

1) Galpha S
2) Galpha I
3) Galpha Q
4) Galpha 12/13

Question 4

Galpha S function

Answer 4

*stimulates cAMP production (adenylyl cyclase converts ATP into cAMP)
*cAMP activates PKA (protein kinase A)

Question 5

Galpha I subunit function

Answer 5

*inhibits cAMP production (inhibits adenylyl cyclase from making cAMP)

Question 6

Galpha Q subunit function

Answer 6

*activates phospholipase C (PLC)
*PLC cleaves PIP2, and IP3 diffuses away
*IP3 releases calcium from smooth ER
*calcium & diacylglycerol activate protein kinase C (PKC)

Question 7

Galpha 12/13 subunit

Answer 7

promotes actin remodeling

Question 8

what are the 3 ways that GPCR signaling must be turned off

Answer 8

1) turn off RECEPTOR
2) turn off Galpha subunit
3) turn off second messenger

Question 9

how do we turn off the GPCR?

Answer 9

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

Question 10

how can we turn off the second messenger?

Answer 10

NEGATIVE FEEDBACK:
-some second messengers stimulate molecules that REMOVE THEM (example: phosphodiesterase is activated by PKA and functions to cleave cAMP)

Question 11

how can we turn off the Galpha subunit?

Answer 11

Galpha subunit has GTPase activity, and therefore turns itself off
*when GTP is bound, subunit is active
*when GDP is bound, subunit is inactive

Question 12

cholinergic receptors

Answer 12

*2 types: nicotinic and muscarinic
*receive Ach

Question 13

adrenergic receptors

Answer 13

*2 types: alpha and beta
*receive norepinephine

Question 14

what amino acid is the precursor for norepinephrine

Answer 14

tyrosine

Question 15

D1 receptors in the sympathetic nervous system

Answer 15

*D1 = dopamine receptor 1
*present on renal vasculature smooth muscle
*receives dopamine

Question 16

alpha 1 receptor

Answer 16

*adrenergic receptor (receives norepinephrine)
*G alpha Q subunit

Question 17

alpha 1 receptor - functions

Answer 17

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

Question 18

alpha 2 receptor

Answer 18

*adrenergic receptor (receives norepinephrine)
*G alpha I subunit

Question 19

alpha 2 receptor - functions

Answer 19

1) inhibit preganglionic sympathetic stimulation
2) inhibit secretion

Question 20

beta 1 receptor

Answer 20

*adrenergic receptor (receives norepinephrine)
*G alpha S subunit

Question 21

beta 1 receptor - functions

Answer 21

1) stimulate JGA renin release
2) INCREASE HR

Question 22

beta 2 receptor

Answer 22

*adrenergic receptor (receives norepinephrine)
*G alpha S subunit

Question 23

beta 2 receptor - functions

Answer 23

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)

Question 24

beta 3 receptor

Answer 24

*adrenergic receptor (receives norepinephrine)
*G alpha S subunit

Question 25

beta 3 receptor - functions

Answer 25

1) increase lipolysis (energy from fat)
2) INHIBIT BLADDER WALLS (stops you from peeing)

Question 26

what receptor is found on sweat glands

Answer 26

M3 (receives Ach but acts as a part of sympathetic response)

Question 27

M1 receptor

Answer 27

*cholinergic receptor (receives Ach)
*G alpha Q subunit

Question 28

M1 receptor - functions

Answer 28

1) higher cognitive functions
2) stimulates enteric nervous system

Question 29

M2 receptor

Answer 29

*cholinergic receptor (receives Ach)
*G alpha I subunit

Question 30

M2 receptor - functions

Answer 30

*SLOWS heart rate

Question 31

M3 receptor

Answer 31

*cholinergic receptor (receives Ach)
*G alpha Q subunit

Question 32

M3 receptor - functions

Answer 32

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

Question 33

metabotropic receptors

Answer 33

*ligand binding alters second messenger, causing a variety of effects
*examples include muscarinic and adrenergic receptors

Question 34

ionotropic receptors

Answer 34

*ligand binding changes conductance (allows ions to flow in/out by opening an ion channel)
*example is nicotinic acetylcholine receptors

Question 35

olfaction - pathway, receptor and channel

Answer 35

*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

Question 36

phototransduction - pathway, receptor, and channel

Answer 36

*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

Question 37

gustation: detection of salty and sour

Answer 37

*direct inflow of cations (either Na+ or H+), depolarizing the cell and releasing the neurotransmission

Question 38

gustation: detection of sweet, bitter, and umami

Answer 38

*GPCRs with G alpha Q subunit