Autonomic (& endocrine) system pharmacology

Question 1

Where are G protein coupled receptors found?

Answer 1

Sit in plasma membrane and have G proteins attached

Question 2

Describe how G protein coupled receptors work

Answer 2

-neurotransmitter (or chemical mediator) binds to it, activating the G protein coupled receptor
-mediates a change in the receptor configuration, activating the G protein
-G protein split into alpha, beta, gamma portions to activate different effectors in cell

Question 3

What effectors can G proteins activate?

Answer 3

-ion channels
-enzymes

Question 3

What are second messengers?

Answer 3

Small diffusible molecules that spread the signal

Question 4

What 2 types of G protein interact with adenylate cyclase?

Answer 4

-G alpha s –> stimulates enzyme
-G alpha I –> inhibits enzyme

Question 5

What is cAMP?

Answer 5

-a second messenger
-moves freely in the cytoplasm

Question 6

What does G alpha S do?

Answer 6

-makes adenylate cyclase more active
-so more cAMP is made
-so more protein kinase A is made (PKA)

Question 7

What do kinases do?

Answer 7

Add phosphates to molecules/proteins

Question 8

What does G alpha I do?

Answer 8

-inhibits adenylate cyclase
-so less cAMP is produced
-so less PKA is produced

Question 9

What does G alpha Q do?

Answer 9

-increases phospholipase C (PLC)
-which increases IP3 + DAG
-IP3 activated receptors on ER membrane to release calcium ions
-increases intracellular Ca2+ and PKA

Question 10

Which G protein subunits mediate the actions of the 3 G proteins?

Answer 10

G alpha S = alpha
G alpha I = alpha, beta + gamma
G alpha Q = alpha

Question 11

What are the agonists and antagonists for muscarinic receptors?

Answer 11

Agonist = muscarine
Antagonist = atropine

Question 12

Where are muscarinic receptors found and how many subtypes are there?

Answer 12

-5 subtypes
-found on postsynaptic ganglion neurons in parasympathetic NS + sweat glands

Question 13

What G proteins do each of the muscarinic receptor subtypes couple to?

Answer 13

-M1, M3, M5 = G Q protein
-M2, M4 = G I protein

Question 14

How do the M1, M3, M5 subtypes of mAChRs work?

Answer 14

-couple with G Q protein
-increases phospholipase C
-increases IP3
-increases intracellular Ca2+
-smooth muscle cells contract + glands secrete

Question 15

How do the M2, M4 subtypes of mAChRs work?

Answer 15

-couple with G I protein
-decreases adenylyl cyclase
-so decreases cAMP
-which increases K+ channel opening (inhibits cell)
-so decrease in voltage gated Ca2+ channels
-decreases excitement of cell

Question 16

What does the M2 and M3 mAChRs do?

Answer 16

M2 = decrease heart rate
M3 = cause gland secretion + muscle contraction

Question 17

Where are M2 receptors found?

Answer 17

In nodal tissue + atria

Question 18

How does the M2 receptor decrease heart rate?

Answer 18

-acetylcholine activates receptor
-G alpha I protein is activated
-beta gamma subunits open K+ channels
-increased K+ moving out of nodal cell
-more -ive membrane potential

Question 19

What are cholinomimetic drugs?

Answer 19

-act directly to enhance cholinergic transmission
-neurotransmitter not broken down = excess stimulation
-acetylcholinesterase drugs are long lasting as they won’t unbind - anticholinesterases

Question 20

What can be used to revere the effects of anticholinesterases?

Answer 20

-muscarinic antagonists
-block receptors that are being stimulated, but not nicotinic receptors

Question 21

What type of receptors are those for noradrenaline and adrenaline and where are they found?

Answer 21

-G protein coupled receptors
-on tissues responding to postganglionic sympathetic neurons

Question 22

What are the subtypes of adrenoreceptors?

Answer 22

-in heart = beta 1
-in bronchi = alpha

Question 23

What do all beta adrenergic receptors couple to?

Answer 23

-G alpha S
-so increase cAMP levels

Question 24

Where are noradrenaline and adrenaline released from in receptor signalling in the heart?

Answer 24

-noradrenaline from sympathetic neurons
-adrenaline from chromaffin cells

Question 25

Where are the beta 1adrenergic receptors in the heart?

Answer 25

-nodal tissue
-ventricular myocytes

Question 26

What does activation of the beta 1 adrenergic receptor lead to?

Answer 26

-activated by noradrenaline
-activates G alpha S protein
-increases adenylyl cyclase
-increase cAMP and PKA
-increases phosphorylation of Ca2+ channels
-increases no. of channels open
-increases Ca2+ into myocytes
-increased contraction

Question 27

What does activation of the beta 2 adrenergic receptor lead to?

Answer 27

-beta 2 receptors on bronchial smooth muscle cells activated by adrenaline
-G alpha S proteins activate
-increases adenylyl cyclase
-increases cAMP and PKA
-increased phosphorylation of smooth muscle cell machinery

Question 28

What are the clinical uses of adrenoreceptor agonists?

Answer 28

-adrenaline = non selective
-used to treat cardiac arrest + anaphylaxis
-beta 2 selective
-used to treat respiratory issues

Question 29

What are the clinical uses of adrenoreceptor antagonists + what unwanted effects can they have?

Answer 29

-used to treat hypertension, heart failure, anxiety
-can cause bronchoconstriction + cardiac depression