Autonomic (& endocrine) system pharmacology Flashcards
Semester 1 year 1
Where are G protein coupled receptors found?
Sit in plasma membrane and have G proteins attached
Describe how G protein coupled receptors work
-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
What effectors can G proteins activate?
-ion channels
-enzymes
What are second messengers?
Small diffusible molecules that spread the signal
What 2 types of G protein interact with adenylate cyclase?
-G alpha s –> stimulates enzyme
-G alpha I –> inhibits enzyme
What is cAMP?
-a second messenger
-moves freely in the cytoplasm
What does G alpha S do?
-makes adenylate cyclase more active
-so more cAMP is made
-so more protein kinase A is made (PKA)
What do kinases do?
Add phosphates to molecules/proteins
What does G alpha I do?
-inhibits adenylate cyclase
-so less cAMP is produced
-so less PKA is produced
What does G alpha Q do?
-increases phospholipase C (PLC)
-which increases IP3 + DAG
-IP3 activated receptors on ER membrane to release calcium ions
-increases intracellular Ca2+ and PKA
Which G protein subunits mediate the actions of the 3 G proteins?
G alpha S = alpha
G alpha I = alpha, beta + gamma
G alpha Q = alpha
What are the agonists and antagonists for muscarinic receptors?
Agonist = muscarine
Antagonist = atropine
Where are muscarinic receptors found and how many subtypes are there?
-5 subtypes
-found on postsynaptic ganglion neurons in parasympathetic NS + sweat glands
What G proteins do each of the muscarinic receptor subtypes couple to?
-M1, M3, M5 = G Q protein
-M2, M4 = G I protein
How do the M1, M3, M5 subtypes of mAChRs work?
-couple with G Q protein
-increases phospholipase C
-increases IP3
-increases intracellular Ca2+
-smooth muscle cells contract + glands secrete
How do the M2, M4 subtypes of mAChRs work?
-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
What does the M2 and M3 mAChRs do?
M2 = decrease heart rate
M3 = cause gland secretion + muscle contraction
Where are M2 receptors found?
In nodal tissue + atria
How does the M2 receptor decrease heart rate?
-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
What are cholinomimetic drugs?
-act directly to enhance cholinergic transmission
-neurotransmitter not broken down = excess stimulation
-acetylcholinesterase drugs are long lasting as they won’t unbind - anticholinesterases
What can be used to revere the effects of anticholinesterases?
-muscarinic antagonists
-block receptors that are being stimulated, but not nicotinic receptors
What type of receptors are those for noradrenaline and adrenaline and where are they found?
-G protein coupled receptors
-on tissues responding to postganglionic sympathetic neurons
What are the subtypes of adrenoreceptors?
-in heart = beta 1
-in bronchi = alpha
What do all beta adrenergic receptors couple to?
-G alpha S
-so increase cAMP levels
Where are noradrenaline and adrenaline released from in receptor signalling in the heart?
-noradrenaline from sympathetic neurons
-adrenaline from chromaffin cells
Where are the beta 1adrenergic receptors in the heart?
-nodal tissue
-ventricular myocytes
What does activation of the beta 1 adrenergic receptor lead to?
-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
What does activation of the beta 2 adrenergic receptor lead to?
-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
What are the clinical uses of adrenoreceptor agonists?
-adrenaline = non selective
-used to treat cardiac arrest + anaphylaxis
-beta 2 selective
-used to treat respiratory issues
What are the clinical uses of adrenoreceptor antagonists + what unwanted effects can they have?
-used to treat hypertension, heart failure, anxiety
-can cause bronchoconstriction + cardiac depression
