Membrane-Bound Receptors

Question 1

What is a receptor?

Answer 1

Protein or group of proteins, usually embedded in cell membrane that allows cell to collect information about its surroundings

Question 2

What is a ligand?

Answer 2

A chemical messenger (small molecule or peptide) that binds and stabilizes conformation of receptor.

Question 3

What is a conformation change?

Answer 3

Change in shape of receptor that induces some downstream signal transduction

Question 4

What are receptors roles in normal physiological processes?

Answer 4

Point of control. Receptor function is regulated by molecules supplied by body.

Question 5

Can a drug make a cell perform a new function it does not normally do?

Answer 5

No

Question 6

What is potency of a drug?

Answer 6

Affinity of the drug for a receptor. I.E. How tightly the receptor binds

Question 7

What is the efficacy of a drug?

Answer 7

The intrinsic activity of the rug; magnitude of drug’s effect.

Question 8

What is an agonist?

Answer 8

Drug combines with receptor to stimulate target organ. Stabilizes the receptor in active conformation.

Question 9

What is an antagonist?

Answer 9

Drug combines with receptor, but interferes with naturally occurring agonist or agonist drug.

• Simply interferes with agonist binding. The normal conformation fluctuation continue as if nothing was there.

Question 10

A ligand that binds to a receptor and activates it is called an _____

Answer 10

agonist

Question 11

A ligand that binds to a receptor and prevents it from activating is called an ____

Answer 11

antagonist

Question 12

What does it mean when a drug binds to an orthosteric site?

Answer 12

Drug acts on main binding site of the receptor. “Traditional” way

Question 13

What does it mean when a drug binds to an allosteric site?

Answer 13

Drug acts on an accessory binding site of a receptor. Stimulates the receptor in a “non traditional” way

Question 14

What is a pore blocker?

Answer 14

Physically obstructs the channel (i.e. ion blocker). Local anesthetics use this as 1 mechanism of action

Question 15

What is the benefit for allosteric drugs?

Answer 15

Tends to be less side effects. It is hard not to overdo it with an orthosteric binding site.

Question 16

Is a receptor in a static state inside the body?

Answer 16

No, the receptor fluctuates between different natural conformations. Some are associated with pharmacological activity, some are not. They can fluctuate between:

1) Active
2) Partially active
3) Inactive

Question 17

What is a partial agonist?

Answer 17

Weakly stabilizes the active state (~50% of time) or stabilize partially active state.

Question 18

What is an inverse agonist?

Answer 18

Holds receptor in inactive state reversing baseline receptor activity. Stabilizes inactive form. AKA Supraantagonist.

Question 19

What is noncompetitive antagonism?

Answer 19

Drug forms covalent bond. No matter what dose you give of agonist, you won’t be able to overcome the antagonist, thereby reducing efficacy.

The higher the dose of antagnoism, the greater decrease in efficacy when agonist given.

Question 20

What is competitive antagonism?

Answer 20

Antagonist that forms weaker bonds (i.e. ionic, van der waals, H bonds). These “pop off and on” the receptor. In this case, when competitive antagonist given, enough dose of agonist drug will allow you to achieve same efficacy.

Most molecules wins in competitive antagonism.

Question 21

What is the location of ligand-gated ion channels?

Answer 21

Membrane

Question 22

How fast does a ligand gated channel act?

Answer 22

Milliseconds

Question 23

Examples of ligand gated ion channel?

Answer 23

Nicotinic ACh receptor GABA(a) receptor

Question 24

What is the effector of ligand-gated ion channels?

Answer 24

Ion channel

Question 25

What is coupling of ligand gated ion channel?

Answer 25

Direct

Question 26

What is the structure of ligand gated ion channels?

Answer 26

Oligomeric assembly of subunits surrounding a central pore

Question 27

What is the location of G-protein coupled receptors on the cell?

Answer 27

Membrane

Question 28

What are the effectors for G-protein coupled receptors?

Answer 28

Channel or enzyme. Usually both at same time

Question 29

What is coupling for g-protein coupled receptors?

Answer 29

G protein or arrestin

Question 30

What are examples of G protein-coupled receptors?

Answer 30

Muscarinic ACh receptor

Question 31

What is the structure of G protein-coupled receptors?

Answer 31

Monomeric or oligomeric assembly of subunits comprising seven transmembrane helices with intracellular G protein-coupling domain

Question 32

What is the location of receptor kinases?

Answer 32

Membrane

Question 33

What is the effector for receptor kinases?

Answer 33

Protein kinases

Question 34

What is the coupling for receptor kinases?

Answer 34

Direct

Question 35

What are examples of receptor kinases?

Answer 35

Insulin, growth factors, cytokine receptors

Question 36

What is the time scale for kinase linked receptors?

Answer 36

Hours

Question 37

What is time scale for G protein coupled receptors?

Answer 37

Seconds

Question 38

What is another name for ligand-gated ion channels?

Answer 38

Ionotropic receptors.

Question 39

What is another name for G protein-coupled receptors?

Answer 39

Metabotropic

Question 40

What is the structure of a receptor kinase?

Answer 40

Single transmembrane helix linking extracellular receptor domain to intracellular kinase domain`

Question 41

Where is location of nuclear receptors?

Answer 41

Intracellular

Question 42

What is effector of nuclear receptors?

Answer 42

Gene transcription

Question 43

What is coupling of nuclear receptors?

Answer 43

Via DNA

Question 44

What are examples of nuclear receptors?

Answer 44

Steroids, birth control

Question 45

What is time scale for nuclear receptors?

Answer 45

Hours

Question 46

What is structure of nuclear receptors?

Answer 46

Monomeric structure with receptor and DNA-binding domains

Question 47

What do ion channels do?

Answer 47

Allow ions to move

Question 48

What is the resting membrane potential of membrane?

Answer 48

Around -70 mV

Question 49

What does excitatory mean?

Answer 49

Inside of cells' charge approaches 0mV - generally by letting positive ions into cell

Question 50

What does inhibitory mean?

Answer 50

Inside of cell's charge becomes more negative -Generally by letting negative (mainly chloride) into the cell. (as well as K out)

Question 51

What are some properties of ligand gated ion channels?

Answer 51

- Fast transmission - Composed of several subunits around central ion pore. * Agonist binding opens pore

Question 52

What are major families of ligand gated ion channels?

Answer 52

- Cys-loop receptors - Ionotropic glutamate receptors

Question 53

Examples of cys-loop receptors?

Answer 53

Nicotinic Ach, 5HT-3 (serotonin) receptors, GABA_a receptors, Glycine receptors, histamine, alcohol (Pentamer structure)

Question 54

Examples of ionotropic glutamate receptors

Answer 54

AMPA NMDA Kainate (tetramer structure)

Question 55

What are cys-loop structures named for?

Answer 55

Loop formed by disulfide bond between two cysteines near N-terminus

Question 56

What are cys-loop receptors made of?

Answer 56

5 subunits around central pore alpha, beta, gamma, delta, epsilon

Question 57

What are examples of excitatory cys-loop receptors?

Answer 57

Nicotinic ACh, serotonin receptors

Question 58

What are examples of inhibitory cys-lop receptors

Answer 58

Glycine, GABA

Question 59

What generally obstructs ion pore in ligand gated channel cys-loop receptors?

Answer 59

Second transmembrane of alpha subunit. Agonist binding changes conformation. moving obstruction and allowing ions to flow through.

Question 60

What are examples of drugs that affect cys-loop receptors?

Answer 60

Nicotinic ACh: Nicotine, Chantix GABAa: Ambien, barbituates, benzos, alcohol

Question 61

What is the reason for coadministration of barbituates, benzos, alcohol being so dangerous?

Answer 61

They all bind to separate sites on GABAa receptors. They do not compete for binding sites, so each additional drug causes inhibition of receptor

Question 62

What are drugs that effect glutamate receptors?

Answer 62

NMDA: Ketamine AMPA: aniracetam (cognition enhancer)

Question 63

What is structure of nicotinic ACh receptors at NMJ?

Answer 63

two alpha (α), one beta (β), gamma (γ), delta (δ) subunit

Question 64

What is structure of channel for neuronal nAChRs

Answer 64

Only alpha and beta

Question 65

What do excitatory nicotinic ACh receptors allow to pass?

Answer 65

Na, K and some Ca ions

Question 66

What do nAChRs do in brain?

Answer 66

Nicotinic ACh receptors upregulate in response to chronic nicotine (like smoking)

Question 67

What are NaChR activation states?

Answer 67

Closed, desensitized, open

Question 68

What are examples of ionotropic glutamate receptors?

Answer 68

AMPS, NMDA, Kainate

Question 69

What do excitatory glutamate receptors allow to pass?

Answer 69

Na, K NMDA can also pass Ca ions

Question 70

What are glutamate receptors comprised of?

Answer 70

* Composed of four subunits * each subunit has four transmembrane domains * second TM domain forms ion pore * Each subunit has binding site- not all binding sites are for glutamate

Question 71

What is required to bind to NMDA receptor for the channel to open?

Answer 71

* 2 Glutamate * 2 glycine * all four must be boudn for channel to open

Question 72

What is long term potentiation?

Answer 72

The more often neuron fires, the stronger the synapse gets -Implicated in learning and memory

Question 73

What is blocking NMDA receptors at RMP?

Answer 73

Mg ion

Question 74

What causes Mg ion blocking NMDA receptors to move?

Answer 74

Depolarization of membrane by AMPA receptors

Question 75

What passes through NMDAr once open?

Answer 75

Ca

Question 76

What happens to Calcium that passes through NMDAr?

Answer 76

Activates CaMKII (Ca-calmodulin kinase II) which leads to more AMPAr's being inserted into synapse. More AMPArs= stronger synapse

Question 77

What is another name for NMDAr's?

Answer 77

"Coincidence detectors" since it requires pre and post synaptic events in order to depolarie.