membrane bound receptors

Question 1

Whats a receptor

Answer 1

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

Question 2

Whats a Ligand

Answer 2

A chemical messenger (can be a small molecule or peptide) that binds and stabilizes a conformation of the receptor…neurotransmitter or Hormone, endogenous substances

Question 3

whats a conformational change

Answer 3

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

Question 4

What regulates receptor function

Answer 4

Regulated by molecules supplied by the body

Question 5

Fyi

Answer 5

Drugs can only mimic or block the body’s own regulatory molecules they will not give a cell new function

Question 6

whats an agonist

Answer 6

the drug combines with a receptor to stimulate target organ
Ligand that binds to a receptor and activates it
Stabilize active conformation

Question 7

whats an antagonist

Answer 7

the drug combines with the receptor, but interferes with a naturally occurring agonist or an agonist drug.
Ligand that bind and disallows the molecules from initiating a repsonse

Interfere with agonist binding. The normal conformation fluctuations continue as if nothing was there

Question 8

what are Pore blockers

Answer 8

Physically obstructs the channel (ion channels)

Question 9

Partial agonist

Answer 9

weakly stabilize the
active state (e.g. ~50%) or
stabilize partially active state

Question 10

What are inverse agonist

Answer 10

stabilize the inactive state reversing baseline/constitutive receptor activity
Stabilizes the inactive form …so u only have inactive form.
xxxInverse agonist actually stabilize the inactive form of the receptor and prevent any endogenous activity…mayb was active a little bit.

A true antagonist, will not knock out little endogenous activity…

Question 11

Properties of receptors Are?

Answer 11

Active
Partially active
Inactive

Drugs can activate or inactivate receptors by stabilizing a pharmacologically significant conformation by binding:
to the same site as the endogenous compound (orthosteric site)
binding to an alternative site (allosteric site)

Question 12

What’s the effect of a competitive antagonist on an Agonist

Answer 12

Effect of a competitive antagonist on the dose-response curve of an agonist.
Note that the maximal response achievable with the agonist is not reduced. Competitive
antagonists simply increase the amount of agonist required to produce any given intensity of
response.

Question 13

What’s the effect of a noncompetitive Antagonist on an Agonist

Answer 13

Effect of a non-competitive antagonist on the dose-response curve of an agonist.
Note that noncompetitive antagonists decrease the maximal response achievable with an agonist.

Question 14

What are the different types of receptors

Answer 14

Ligand-gated ion channels…nicotinic receptors
G-protein coupled receptors….7 transmembrane receptors span the membrane 7 times…composed of:receptor/g protein/effector…taste
Kinase-linked receptors…intracellular and extracellular domain
Nuclear receptors. Not cell membrane-bound…located in the cytoplasm…so it’s lipophilic

Question 15

Ligand Gated characteristics ARe?

Answer 15

Location: Membrane
Effector: ion
Coupling: Direct
 This is a fast transmitting channel
Composed of several subunits arranged around a central ion pore
Agonist binding opens pore

Nicotinic, Ach,Gaba A receptor

Question 16

Excitatory Vs Inhibitory response

Answer 16

Resting membrane potential: Inside of the cell has an overall negative charge of ~-70 mV
Excitatory: means that the inside of the cell’s charge approaches 0 mV
Generally by letting positive ions into the cell
Inhibitory: means that the inside of the cell’s charge becomes more negative
Generally by letting negative ions (mainly chloride) into of the cell

Gaba receptors influence chloride conduction thereby inhibitory
Potassium also can leave cell and making it also negative

Question 17

What are the Major family of the Ligand-gated ion chanel

Answer 17

Cys-loop receptors: nicotinic acetylcholine receptor, glycine receptors, 5HT-3 receptor, etc. only excitatory present here

Ionotropic Glutamate Receptors: AMPA receptor, NMDA receptor, kainate receptor

Question 18

components of Cys-Loop receptors

Answer 18

Named for the loop formed by the disulfide bond between two cysteines near the N-terminus
Made of five subunits arranged around a central pore
Five types of subunits: α, β, γ, δ, ε
Excitatory: Nicotinic acetylcholine receptors

Question 19

how does gating occur with Cysa-loop receptors

Answer 19

The second transmembrane domain of the α subunit generally obstructs the ion pore
Agonist binding changes the conformation, moving the obstruction and allowing ions to flow through

the two Ach molecules are the Agonist and both need to bind.

Question 20

Types of Cys-loop receptors are

Answer 20

Nicotinic acetylcholine receptors: Nicotine, Varenicline (Chantix)
GABAA receptors: Ambien (zolpidem)Barbituates, benzodiazepines, alcohol

Question 21

Characteristics of Nicotinic acetylcholine receptors

Answer 21

Exist at the neuromuscular junction (NMJ) and in the CNS
NMJ nAChR contains a, β, δ, and γ subunits
Neuronal nAChRs contain only a and β subunits
Excitatory
Pass Na+, K+, and some Ca++ ions
Composed of five subunits
In the brain, nAChRs upregulate in response to chronic nicotine (like smoking)
2 ach molecules bind to open the nicotine receptors

Nicotine receptors…when u are chronically exposed there is an upregulation to receptors. This is the reason it is so difficult to stop smoking when u start

Question 22

Nachr HAs 3 activation states namely?

Answer 22

Desensitized, closed and open

Question 23

Ionotropic Glutamate receptors compose of

Answer 23

AMPA receptors, NMDA receptors, and Kainate receptors
Excitatory
Pass Na+ and K+ ions
NMDA receptors can also pass Ca++ ions
Composed of four subunits
Each subunit has four transmembrane domains
Second TM domain forms the ion pore
Each subunit has a binding site-not all binding sites are for glutamate
NMDA receptor: two binding sites for glutamate, two binding sites for glycine
All four binding sites must be occupied for the channel to open

Question 24

Explain the process of long term potentiation

Answer 24

Long Term Potentiation (LTP): the more often a neuron fires, the “stronger” the synapse gets
Implicated in learning and memory

At resting membrane potential, NMDA receptors are blocked by Mg++
Magnesium block is voltage-dependent
Depolarization of neuron relieves the block, allows NMDAR to open
NMDARs pass Ca++, which activates CaMKII(calmodulin kinase II), which leads to AMPARs inserted into the synapse
More AMPARs = stronger synapse

Question 25

Gprotein coupled receptors characteristics

Answer 25

Location: Membrane
Effector: Chanel or enzyme
coupling:G-protein or Arrestin
e.gsMuscarinic acetylcholine receptors, Adrenoceptors.

Slower signaling than ligand-gated ion channels
Rely on second messengers for signaling
~3% of our genome dedicated to GPCR coding
Target for more than half of current pharmaceuticals

Question 26

3main classes of Gprotein receptors

Answer 26

Class A: adrenergic receptors, muscarinic acetylcholine receptors
Class B: Parathyroid Hormone receptor
Class C: metabotropic glutamate receptors, GABAB receptors

Question 27

Ga subunits for G protein are ?

Answer 27

Gαs  activation of adenylyl cyclase and increase in cAMP
Gαi  inhibition of adenylyl cyclase and decrease in cAMP
Gαq  activation of phospholipase C, phosphoinositol hydrolysis, increase in IP3 and DAG, and release of Ca2+ from intracellular stores

Question 28

What are the target enzymes for Gprotein

Answer 28

Guanylate cyclase
Adenylate Cyclase
Phospholipase C

Question 29

Gportein Effectors are:

Answer 29

Enzymes and transport proteins,Contractile proteins,Ion channels

Question 30

Explain GPCR Desensitization

Answer 30

If a ligand is bound onto a GPCR for a prolonged period of time, β-arrestin binds to the receptor, thus tagging it for internalization
Contributes to drug tolerance
The GPCR-β-arrestin complex can act as a protein scaffold inside the cell
Independent of G protein signaling