38 - Receptors

Question 1

What type of Agonism do ARB’s Exhibit?
–> AT1R

Answer 1

• *INVERSE AGONISM**
• though they are called AT2 Receptor ANTAGONIST*

Ligand-INDEPENDENT activation
&
lingand-mediated

Question 2

RECEPTORS
Definition & Role

Answer 2

• *Cell-Surface Recognition sites** for:
• *hormotes / NT’s / neuromodulators**

which are coupled to various
Signal Transduction cascades
can regulate cellular responses in phys/patho processes

LIGANDS
are what binds to receptors

Question 3

Similarities of
GPCRs & Ion Channels

Answer 3

Activation leads to
CONFORMATIONAL CHANGE
of the protein

Question 4

Why do ARBs (-sartans) do NOT cause the
cough side effect like ACE-I (captopril)?
(GPCR target vs Hydrolase)

Answer 4

Sartans are SELECTIVE for
TYPE 1 AT2 Receptor

ACE also breaks down
Bradykinin (cytokine)
so ACE-Inhibitors PREVENT this breakdown
leading to COUGH

Question 5

MAIN group of RECEPTORS
as DRUG TARGETS

Answer 5

GPCRs
activated by ligands:
ions / NT’s / peptides / proteins
or sensory agents:
photons / touch / taste / smell

Question 6

Inverse Agonist

Answer 6

By adding MORE DRUG there is a
REDUCTION in response

NEGATIVE INTRINSIC ACTIVITY

Question 7

What DRUG targets GPCRs = receptors?

Indication // Name of receptor

Answer 7

SARTANS
Losartan = Cozaar

Angiotensin 2 - Type 1 Receptor Blockers = ARB
a GPCR

used for Hypertension

Question 8

GPCRs FUNCTION

Answer 8

Activation of GPCR is fundamental:
promotes Intracellular signaling in numerous
Physiological & Pathological processes
VVVV
Important tools in COMBATING DISEASE

Question 9

What are Common Features
on the Chemical structure of SARTANS (ARBs)?

Answer 9

BIPHENYL

IMIDAZOLE

TETRAZOL

B-I-T

Question 10

DIFFERENCES of

GPCRs & Ion Channels

Answer 10

Receptor vs Channel (transporter)

• *GPCR**
• *Signal Transduction Cascades** –> Seconds to minutes
• *Ion Channels**
• *open pores** –> electrical current
• *FAST RESPONSE –> MILLISECONDS**

Question 11

What are the CRITICAL 3 Residues
in which SARTANS bind/dock to AT1R?

AT2 Type 1 Receptor = GPCR

Answer 11

AT&T

Arg167

Trp84

Tyr35

binding to more of these residues –> higher affinity

Question 12

Antagonist

Answer 12

ZERO INTRINSIC ACTIVITY

production STOPS not LESS

Question 13

lower the Kd

how does it effect the affinity?

Answer 13

GREATER AFFINITY

• *Kd = DISSOCIATION constant**
• *@Kd** we are at HALF occupency

NEED LESS DRUG to be HALF OCCUPIED