Autonomic nervous system Flashcards
Sequence of events used to understand each of the GPCR systems?
first messenger to G-protein coupled receptor to effector to second messenger to cellular response
What is the first messenger?
ligand that binds to the GPCR
What can the first messenger be?
This ligand could be something endogenous to the body like a neurotransmitter or hormone or something exogenous to the body like a drug
Where does the G protein reside? Where is the receptor?
The receptor is accessible outside of the cell membrane.
The G-protein itself resides inside of the cell membrane.
What subunits does the G-protein have?
alpha
beta
gamma
What is the function of the G protein?
The G protein either stimulates or inhibits an effector (enzyme or ion channel).
Tell me about G stimulatory proteins?
They turn on an effector and are Gs and Gq proteins
What do G inhibitory proteins do?
They turn off an effector (Gi)
What happens when a ligand binds to the GPCR? (4 steps)
- The ligand- receptor interaction activates the G protein.
- This causes the alpha subunit to dissociate from the beta and gamma subunits.
- The alpha subunit of the Gs or Gq protein will turn on an effector, while the alpha subunit of the Gi protein will turn off an effector.
- When the ligand unbinds from the receptor, the alpha subunit rejoins the beta and gamma subunits, and its interaction with the effector ends.
What is the function of the effector?
To activate the second messenger
You have enzymatic effectors and ion channel effectors, name them?
enzymatic = adenylate cyclase and phospholipase C
Ion channel effectors = GABA-A and M2 receptor at the SA node
What does the second messenger do?
modulates a network of enzymatic activity, including phosphatases and protein kinases. This governs a complex series of intracellular reactions that elicit a specific response within a particular cell type.
Is the response to the 2nd messenger one and done or large in scale?
The 2nd messenger allows for signal amplification.
What is signal amplification (caused by 2nd messenger)
signal amplification is a process that allows a single molecule to initiate a process that activates a large number of physiologic changes - each step progressively increases the magnitude of the response.
The intracellular response to a 2nd messenger is tissue specific… what does this mean?
increased cAMP (or whatever it is stimulating or inhibiting) may cause different effects in different cell types
Five 2nd messengers you should know?
cAMP cGMP IP3 DAG CA+2
cyclic adenosine monophosphate is cAMP
cyclic guanosine monophosphate is cGMP
Inositol triphosphate is IP3
Diacylglycerol is DAG
Calcium ion is Ca+2
Is glutamate a first or second messenger?
first messenger for NMDA receptor
Name the receptors whos signal transduction is inhibitory (3 of them)
Alpha 2
Muscarinic 2 /4
Dopamine 2 (presynaptic)
Alpha 2, M2 and M4, and Dopamine 2 are all inhibitory signal transduction. What is the effector and 2nd messenger details?
decreased adenylate cyclase and decreased cAMP
Name as many receptors as you can?
Alpha 1 and 2 Beta 1 and 2 Nicotinic Muscarinic 1,2,3,4, and 5 Dopamine 1 and 2 Vasopressin 1 and 2 Histamine 1 and 2
Phospholipase C and Adenylate cyclase applies to which step in the GSCP sequence?
a) signal transduction
b) receptors
c) second messengers
d) effectors
d) effectors
Which receptors are Gs and increase adenylate cyclase and cAMP?
B1, B2
D1
V2
H2
Which receptors are Gq and increase phospholipase C which increases IP3, Ca+2, and DAG?
Alpha 1
M 1, 3, 5
V1
H1
SNS receptor for the myocardium and conduction system?
B1
PNS receptor for the myocardium and conduction system?
M2
Action of SNS stimulation on the myocardium?
increased contractility
Action of SNS stimulation on the conducting system? (2)
increased heart rate
increased conduction speed
Action of PNS stimulation on the myocardium?
Decreased contractility
Action of PNS stimulation on the conducting system? (2)
decreased HR
decreased CV
SNS receptor of the arteries and veins?
arteries = a1> a2
veins = a2> a1
action of SNS receptor stimulation on the arteries and veins?
vasoconstriction
SNS receptor of the myocardium and skeletal muscle vascular beds?
B2
SNS receptor of the Renal and Mesenteric vascular beds?
DA
Action of SNS stimulation to the myocardium, skeletal muscle, renal, and mesenteric vascular beds?
Vasodilation
SNS receptor of the Bronchial tree?
B2
PNS receptor of the Bronchial Tree?
M3
action of SNS receptor to the bronchial tree?
What about PNS receptor action?
Bronchodilation when the SNS is activated
Bronchoconstriction when the PNS is activated
What is the SNS receptor of the renal tubules?
a2
action of SNS receptor on the renal tubules?
Diuresis (ADH inhibition)
Which SNS receptor in the kidneys is responsible for Renin release?
B1
When B1 SNS receptor is activated in the kidney what happens?
increased renin release
When talking about the eye, alpha 1 stimulation causes what to happen?
radial muscle contraction which leads to mydriasis or pupil dilation
When talking about the eye Muscarinic stimulation causes what to happen?
sphincter muscle contraction leading to miosis or pupil constriction
Alpha 2 receptors are present throughout the body, what are the 3 classifications of location?
presynaptic
postsynaptic
nonsynaptic
stimulation of which receptor reduces SNS outflow and produces sedation, hypnosis, and analgesia?
alpha-2
What are the traditional effects of giving Precedex?
reduction in SNS causing sedation, MAC reduction, analgesia, bradycardia, and vasodilation
If you rapidly administer Precedex what may occur?
stimulation of the postsynaptic alpha 2 receptors in the arterial and venous circulation leading to vasoconstriction and hypertension… Transient rise in blood pressure
Precedex is centrally acting, what does this mean?
working on the central nervous system
What is the effector that converts ATP to cAMP?
Adenylate cyclase
Which enzyme metabolizes cAMP (turns it off)?
Phosphodiesterase III
In the presence of oxygen how many moles of ATP can be produced from 1 mole of glucose?
38 moles
Reuptake of NE into the presynaptic nerve is inhibited/blocked by what two things?
tricyclic antidepressants and cocoaine
Which two enzymes break down NE?
MAO
COMT
Primary transmitter in the parasympathetic nervous system?
Acetylcholine
In the presence of which enzyme does choline and acetyl CoA join to form acetylcholine?
choline acetyltransferases
what is an antagonist of calcium at the presynaptic nerve terminal?
magnesium
Is Ach reused and reuptaked?
No
How is Ach done away with once it unbinds from its receptor?
Acetylcholinesterase (true cholinesterase) is positioned around the cholinergic receptors and quickly hydrolyzes Ach after it unbinds from the receptors.
What substance is taken back into the nerve terminal after acetylcholinestersase hydrolyzes Ach?
Choline
acetate diffuses away from the synaptic cleft
alpha 1 stimulation to the eye, specifically the radial muscle causes what?
contraction (mydriasis)
B2 stimulation of the eye, specifically the ciliary muscle causes what?
relaxation (far vision)
M receptor stimulation of the sphincter muscle in the eye (iris) causes what?
contraction (miosis)
Islet (B cells) in the pancreas, when the A2 receptor is stimulated vs the B2 receptor what happens?
alpha 2 = decreased insulin release (higher blood sugar)
beta 2 = increased insulin release (lower blood sugar)
Which SNS receptor when stimulated always causes some form of constriction?
alpha 1
