G Protein Coupled Receptor Signaling

Question 1

[1] Signaling:
- signaling cell is very distant from the target cell
- the ligand (hormone) must travel through the blood stream in order to reach its target
[2] Signaling
- two adjacent, but different type, cells signaling to each other
[3] Signaling
- the target site for a signal molecule is on the same cell
- signaling to adjacent call (same type of cell)

Answer 1

[1] Endocrine
[2] Paracrine
[3] Autocrine

Question 2

GPCR Activation/Inactivation:

• hormone binds to receptor and induces conformational change with a higher affinity for the [1]
• this binding activates the [2] function and the GDP is shed away and replaced by GTP
• this triggers the dissociation of the [3] subunit away and has a high affinity for [4]
• GDP restored and subunits recombine

Answer 2

[1] G-Protein
[2] GEF
[3] alpha
[4] effector (membrane)

Question 3

One of the most common effector molecules is called [1]. Its second messenger is [2] which activates [3].

Activated by epinephrine, glucagon, and ACTH
Inhibited by PGE1 and adenosine

Answer 3

[1] Adenylyl Cyclase
[2] cAMP
[3] Protein Kinase A

Question 4

Secondary Messengers:
[1] activates protein kinase A
[2] activates protein kinase G and opens channels in rod cells
[3] activates protein kinase C
[4] opens calcium channels in the ER

Answer 4

[1] cAMP
[2] cGMP
[3] DAG (1,2-Diacylglycerol)
[4] IP3 (Inositol 1,4,5-triphosphate)
[4]

Question 5

Bacterial Activation/Inactivation of GPCR
1. Cholera
modification of [1] subunit
PKA activity increased leading to increased [2] activity
chlorine and water loss leading to watery diarrhea
2. Whooping Cough
modification of the [3] subunit
[4] CFTR activity leading to mucous secretion in lungs

Answer 5

[1] Galpha stimulatory (stuck in the on position)
[2] CFTR (chlorine channel)
[3] Galpha inhibitory (prevents GDP release)
[4] increased

Question 6

68 year old woman with tightness in her chest
short of breath while walking
lack of energy
BAD EKG (heart failure)
There may be bad [1] signaling.

Answer 6

[1] Beta-Adrenergic

Question 7

Normal Cardiac Contraction
Beta-Adrenergic signaling leads to calcium release from the sarcoplasmic reticulum into cytosol (systolic)
calcium efflux into SR causes muscle relaxation (diastolic)
strength of beat ratio between [1]
In heart failure, there is [2] beta-adrenergic signaling which decreases the ratio of calcium in cytosol

Answer 7

[1] cystolic:SR calcium levels

[2] increased

Question 8

A beta-blocker such as the drug [1] will inhibit excess beta-adrenergic (beta-AR) signaling. This helps reestablish proper cytosolic:SR ratios of calcium stores

Answer 8

[1] Propranolol

Question 9

Endothelial Cell Signaling to Smooth Muscle (Endocrine to Paracrine):
Acetylcholine binds to a G-coupled receptor in smooth muscle. This activates the secondary effector phospholipase C with leads to [1] activation/cleavage. This modulates [2] which directly impacts [3] leading to the synthesis of nitric oxide (NO). This binds to NO receptor which creates [4] that activates protein kinase G and leads to relaxation.

Answer 9

[1] IP3
[2] Calmodulin
[3] NO synthase
[4] cGMP