ANS & Endocrine with pharmacology Flashcards
What happens when G proteins are activated?
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
What are the 2 enzymes G proteins can activate or inhibit?
Adenylyl cyclase and phospholipase C
*whether you activate or inhibit them will change the amount of second messengers that are produced
What are second messengers?
Small diffusible molecules that spread the signal
What are the 2 G proteins that interact with adenylyl cyclase?
Ga(s) stimulates adenylyl cyclase
Ga(i) inhibits adenylyl cyclase
What happens when Ga(s) binds to adenylyl cyclase?
It stimulates it and makes it more active
MAKES more cAMP
Increases the amount of protein kinase A (PKA) levels
What does cAMP stand for and what is it?
Cyclic AMP
It is a second messenger that moves freely in the cytoplasm
What are kinases?
Add phosphates to molecules/proteins
What happens when Ga(i) binds to adenylyl cyclase?
It decreases the activity of adenylyl cyclase
Makes less cAMP
Decreases the amount of protein kinase A (PKA) levels
What is Ga(q)?
It increases intracellular Ca2+ levs through the enzyme phospholipase C
how does Ga(q) work?
Increase phospholipase C (PLC)
increase IP3 + DAG (diacyl glycerol)
increase Ca2+ inside cell + increases PKA
What agonist and Antagonist affect muscarinic receptors?
Agonist: Muscarine
Antagonist: Atropine
How do M1, M3, and M5 function?
*odd numbers are coupled to Ga(q)
They affect the Ga(q)
-increase PLC
-increase IP3
-increase intracellular Ca2+
What do M2, and M4 do?
*even numbers are coupled to Ga(i)
Affect Gai
-decrease Adenylyl cyclase
-decrease cAMP
-increase K+ channel opening
-decrease voltage gated Ca2+ channels
What happens when muscles or gland have activated M1,M3 or M5 on them?
Calcium levels will increase and cause contraction or secretion
Are M2 and M4 receptors likely to be inhibitory or stimulatory?
Inhibitory
Its likely the activity of the call will decrease with these receptors coupled to it
Where are M2 receptors located and what is their response when activated?
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)
Explain the pathway that decreases heart rate via M2 receptor activation
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
M1 and M3 AChR’s are Gq coupled receptors. What do they do?
Stimulate contraction of smoot muscle
-bronchoconstriction
-bladder voiding
Stimulate secretion from exocrine glands
-mucus in the lungs
-salivary glands
sweat glands
what is muscarine?
Muscarine is the main agonist drug that can activate all muscarinic ACh receptors
what effects can muscarine have when taken?
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
What is atropine?
Atropine is a non-selective mAChR antagonist drug that inhibits secretion
What is acetylcholinesterase (AChE)?
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
What does cholinomimetic mean?
It mimics the effects of having excess ACh
Where are B1 and B2 receptors found?
B1- heart
B2- bronchi
What do all Beta androgenic receptors couple to?
Ga(s) and therefore increase cAMP
Does the parasympathetic or sympathetic NS have more control over contractility?
Sympathetic
Does receptor signalling via Ga(s) in the heart cause an increased heart rate and contractility?
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
What is noradrenaline?
Ats as both a hormone and a neurotransmitter in the human body. It plays a crucial role in the fight-or-flight response
Explain the cascade of reactions that happen in the heart when B1 is activated
*IN THE HEART
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
Explain the cascade of reactions that happen in the heart when B2 is activated
*IN THE LUNGS
B2 activation on bronchial smooth muscle cell via adrenaline
+ adenylyl cyclase
+cAMP
+PKA (causing smooth muscle relaxation)
+ phosphorylation of smooth muscle cell machinery
Why is salbutamol used in inhalers?
*adrenoreceptor agonists
Salbutamol contains B2 selective agonists which carry out a cascade of reactions to avoid cardiovascular consequences associated with B1 effects
Why is adrenaline used during cardiac arrest and anaphylaxis?
*adrenoreceptor agonists
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
When can adrenoreceptor antagonists be used?
-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.
