ANS & Endocrine with pharmacology

Question 1

What happens when G proteins are activated?

Answer 1

They split into their Alpha and Beta part and go on to affect different parts of the cell.
*The effects can be on ion channels or enzymes

Question 2

What are the 2 enzymes G proteins can activate or inhibit?

Answer 2

Adenylyl cyclase and phospholipase C
*whether you activate or inhibit them will change the amount of second messengers that are produced

Question 3

What are second messengers?

Answer 3

Small diffusible molecules that spread the signal

Question 4

What are the 2 G proteins that interact with adenylyl cyclase?

Answer 4

Ga(s) stimulates adenylyl cyclase
Ga(i) inhibits adenylyl cyclase

Question 5

What happens when Ga(s) binds to adenylyl cyclase?

Answer 5

It stimulates it and makes it more active
MAKES more cAMP
Increases the amount of protein kinase A (PKA) levels

Question 6

What does cAMP stand for and what is it?

Answer 6

Cyclic AMP
It is a second messenger that moves freely in the cytoplasm

Question 7

What are kinases?

Answer 7

Add phosphates to molecules/proteins

Question 8

What happens when Ga(i) binds to adenylyl cyclase?

Answer 8

It decreases the activity of adenylyl cyclase
Makes less cAMP
Decreases the amount of protein kinase A (PKA) levels

Question 9

What is Ga(q)?

Answer 9

It increases intracellular Ca2+ levs through the enzyme phospholipase C

Question 10

how does Ga(q) work?

Answer 10

Increase phospholipase C (PLC)
increase IP3 + DAG (diacyl glycerol)
increase Ca2+ inside cell + increases PKA

Question 11

What agonist and Antagonist affect muscarinic receptors?

Answer 11

Agonist: Muscarine

Antagonist: Atropine

Question 12

How do M1, M3, and M5 function?
*odd numbers are coupled to Ga(q)

Answer 12

They affect the Ga(q)
-increase PLC
-increase IP3
-increase intracellular Ca2+

Question 13

What do M2, and M4 do?
*even numbers are coupled to Ga(i)

Answer 13

Affect Gai
-decrease Adenylyl cyclase
-decrease cAMP
-increase K+ channel opening
-decrease voltage gated Ca2+ channels

Question 14

What happens when muscles or gland have activated M1,M3 or M5 on them?

Answer 14

Calcium levels will increase and cause contraction or secretion

Question 15

Are M2 and M4 receptors likely to be inhibitory or stimulatory?

Answer 15

Inhibitory
Its likely the activity of the call will decrease with these receptors coupled to it

Question 16

Where are M2 receptors located and what is their response when activated?

Answer 16

Located in the atria and nodal tissue of the heart
Causes cardiac inhibition (reduces heart rate)
slowing of atrioventricular conduction
decreased force of contraction (atria only)

Question 17

Explain the pathway that decreases heart rate via M2 receptor activation

Answer 17

M2 is activated by ACh
Ga(i) protein activation
Beta subunit opens K+ channel
more K+ moves OUT of the nodal cell
More negative membrane potential

Question 18

M1 and M3 AChR’s are Gq coupled receptors. What do they do?

Answer 18

Stimulate contraction of smoot muscle
-bronchoconstriction
-bladder voiding

Stimulate secretion from exocrine glands
-mucus in the lungs
-salivary glands
sweat glands

Question 19

what is muscarine?

Answer 19

Muscarine is the main agonist drug that can activate all muscarinic ACh receptors

Question 20

what effects can muscarine have when taken?

Answer 20

When muscarine is taken, all the muscarinic receptors will be activated meaning that all the different responses happen. This means it isn’t very helpful clinically as it isn’t very specific to one receptor

Responses include –blood pressure, +saliva, +tear flow and +sweating

Question 21

What is atropine?

Answer 21

Atropine is a non-selective mAChR antagonist drug that inhibits secretion

Question 22

What is acetylcholinesterase (AChE)?

Answer 22

It is an enzyme that breaks down ACh.
acetylcholinesterase drugs such nerve gas (sarin) are irreversible meaning that they cannot unbind once they are bound to the AChE

Question 23

What does cholinomimetic mean?

Answer 23

It mimics the effectshaving excess ACh

Question 24

Where are B1 and B2 receptors found?

Answer 24

B1- heart
B2- bronchi

Question 25

What do all Beta androgenic receptors couple to?

Answer 25

Ga(s) and therefore increase cAMP

Question 26

Does the parasympathetic or sympathetic NS have more control over contractility?

Answer 26

Sympathetic

Question 27

Does receptor signalling via Ga(s) in the heart cause an increased heart rate and contractility?

Answer 27

Yes as noradrenaline from Sympathetic neurons and adrenaline from chromaffin cells bind to receptors on the nodal tissue.
the androgenic receptors (B1) are found in ventricular myocytes

Question 28

What is noradrenaline?

Answer 28

Ats as both a hormone and a neurotransmitter in the human body. It plays a crucial role in the fight-or-flight response

Question 29

Explain the cascade of reactions that happen in the heart when B1 is activated
*IN THE HEART

Answer 29

Sympathetic neurons released noradrenaline
B1 is activated by noradrenaline
Ga(s) protein is activated
+ adenylyl cyclase
+ cAMP
+ PKA
+ Phosphorylation of calcium channels
*happens in ventricular myocytes
+ calcium channels open time
+calcium into myocytes
SO INCREASED CONTRACTION

Question 30

Explain the cascade of reactions that happen in the heart when B2 is activated
*IN THE LUNGS

Answer 30

B2 activation on bronchial smooth muscle cell via adrenaline
+ adenylyl cyclase
+cAMP
+PKA (causing smooth muscle relaxation)
+ phosphorylation of smooth muscle cell machinery

Question 31

Why is salbutamol used in inhalers?
*adrenoreceptor agonists

Answer 31

Salbutamol contains B2 selective agonists which carry out a cascade of reactions to avoid cardiovascular consequences associated with B1 effects

Question 32

Why is adrenaline used during cardiac arrest and anaphylaxis?
*adrenoreceptor agonists

Answer 32

cardiac arrest- when heart isn’t functioning properly, a shot of adrenaline will stimulate the B1 receptors

anaphylaxis- during allergic reaction bronchioles constrict and you’re struggling to breathe, EpiPen with adrenaline will activate the B2 receptors

Question 33

When can adrenoreceptor antagonists be used?

Answer 33

-Hypertension
-Heart failure
-Anxiety

WHY?
Adrenoreceptor antagonists work by binding to adrenoreceptors in the heart, blood vessels, and other tissues, preventing adrenaline and noradrenaline from activating them.