Membrane bound receptors

Question 1

ligand

Answer 1

a chemical messenger that induces a conformational change in the receptor

Question 2

conformational change

Answer 2

change in the shape of a receptor that induces some downstream signal transduction

Question 3

two types of receptors

Answer 3

ligand gated

G protein-coupled receptors

Question 4

resting membrane potential

Answer 4

about -70mV

Question 5

inhibitory ions

Answer 5

Cl^- into cell

K⁺ out of cell

Question 6

excitatory ions

Answer 6

Na and Ca into cell

Question 7

agonist

Answer 7

ligand that binds to a receptor, thereby activating it

**a high concentration of antagonist can out-compete and agonist

Question 8

antagonist

Answer 8

a ligand that binds to a receptor that prevents it from activating

**a high concentration of agonist can out-compete an antagonist

Question 9

orthosteric antagonist

Answer 9

a ligand or drug that acts on the main binding site of the receptor

Question 10

allosteric antagonist

Answer 10

a ligand or a drug that binds to an accessory binding site of the receptor, maybe causing a conformational change??

Question 11

Ligand gated channels

Answer 11

• fast
• composed of several subunits arranged around a central ion pore

Question 12

major families of ligand-gated channels

Answer 12

1. cys-loop receptors
2. ionotropic glutamate receptors

Question 13

Cys-loop receptors

Answer 13

• Named because they have a characteristic loop of an amino acid chain between two cystein residues which form a disulfide bond.
• made of 5 subunits arranged around a central pore
  
  • usually 2 alpha
  • beta, gamma, delta, or epsolon
• Part of the alpha subunit closes off the channel until a ligand binds and changes the conformation, moving the blockage and allowing ions to flow through

Question 14

Ionotropic glutamate receptor examples and drugs

Answer 14

1. AMPA receptor
   
   1. aniracetam
2. NMDA receptor
   
   1. ketamine
3. Kainate receptor

Question 15

Cys loop excitatory receptors and drugs

Answer 15

1. Nicotinic acetylcholine receptors
   
   1. Nicotine
   2. Varenicline (Chantix)
2. serotonin receptors

Question 16

Cyc-loop inhibitory receptors and drugs

Answer 16

• glycine
• GABA
  
  • Ambien
  • barbituates
  • benzodiazepines
  • alcohol

Question 17

Nicotinic Acetylcholine receptors

Answer 17

• Exist at the neuromuscular junction (NMJ) and in the CNS
• Composed of 5 subunits
  
  • NMJ nAChR contain alpha, beta, delta and gama subunits
  • Neuornal nAChRs contain only alpha and beta subunits
• Excitatory- pass Na+, K+, and some Ca++ ions
• In the brain, nACjrs upregulate in response to chronic nicotine (like smoking)

Question 18

Ionotropic Glutamate Receptors

Answer 18

• Excitatory
  
  • pass Na+ and K+ ions
  • NMDA receptors can also pass Ca++
• tentamer- 4 subunits
  
  • each subunit has a binding site
    
    • not all binding sites are for mlutamate
  • NMDA receptor: tow binding sites for glutamate, two sites for glycine
  • All four binding sites must be occupied for the channel to open

Question 19

Long term potentiation

Answer 19

• the more often a neuron fires, the “stronger” the synapse gets
• At resting membrane potential, Mg++ blocks NMDA receptors
  
  • Mg block is voltage dependent
  • Depolarization of neuron relieves the block, allows NMDAR to open
• NMDARs pass Ca, which activates CamKII
  
  • CaMKII inserts additional AMPA receptors into surface of synaps which causes a stronger response

Question 20

Class A

G Protein-Coupled receptors

Answer 20

1. adrenergic receptors
2. muscarinic acetylcholine receptors

Question 21

Class B

G Protein-Coupled receptors

Answer 21

parathyroid hormone receptor

Question 22

Class C

G Protein-Coupled Receptor

Answer 22

1. metabotropic glutamate receptors
2. GABA receptors

Question 23

G_alpha-S

Answer 23

activation of adenylyl cyclase and increase in cAMP

Question 24

G_{alphi I}

Answer 24

inhibition of adenylyl cyclase and decrease in cAMP

Question 25

G_{alpha q}

Answer 25

activation of phospholipase C, phosphoinositol hydrolysis, increase in IP₃, and DAG and release of Ca++ from ER

Question 26

Cholera Toxin Mechanism

Answer 26

1. cholera toxin is internalized by the cell
2. disrupts conversion of GTP to GDP
   
   1. G_alphaS is unable to inactivate the GTP into GDP, increasing GTP concentration.
3. Increased level of GTP leads to abnormally high cAMP levels
   
   1. cAMP activate Cl^- pumps, which release more Cl^- into the intestinal lumen
   2. Na, K, and HCO₃ follow, then leading to more water remaining in intestine to balance the osmolarity, causing diarrhea

Question 27

G Protein-coupled receptor desensitization

Answer 27

• to turn off response or adapt to persistent stimuli
• Beta-arrestin binds to the receptor, tagging it for internalization
  *