Lectures 17 & 18 Neurotransmitters and Neuromodulators Flashcards
What type of receptor are cholinergic N1 and N2 receptors?
ionotropic
What is PDE? What is its action?
PDE- Phosphodiesterase
it breaks down cAMP into 5’ AMP
What effector protein is activated by G-S?
Adenylyl cyclase (AC)
What does Adenylyl cyclase do?
AC produces cAMP from ATP
What enzyme can produce cAMP from ATP?
Adenylyl cyclase
How is cAMP action terminated?
breakdown by phosphodiesterase (PDE)
What are 2 ways that the concentration of cAMP can be regulated?
- rate of synthesis by adenylyl cyclase (AC)
2. breakdown by phosphodiesteras (PDE)
What does cAMP do? How is it made?
cAMP can activate and ion channel or another protein
It is made by adenylyl cyclase from ATP (AC is activated by a G-S protein)
What happens to a g protein when GDP is exchanged for GTP?
it becomes activated
alpha subunit dissociates from beta-gamma subunit and they both go to interact with efferectors
How are G-proteins inactivated?
the alpha sub-unit hydrolyzes the GTP back to GDP and the alpha, beta and gamma units again form a trimer (inactive)
How does caffeine affect phosphodiesterase (PDE)?
decreases PDE thus increasing effects of cAMP
How does G-C work?
activates guanylate cyclase to generate cGMP (similar to G-s that generates cAMP)
How does G-i work?
decreases adenylyl cyclase activity and thus decreases cAMP production–>inhibition/modulation of ion channels (alpha-2 autoreceptors work in this manner-NE)
What do G-q proteins activate?
phospholipase C (PLC)
What 2 second messengers are produced as a result of PLC activation by Gq?
IP3 and DAG
What does IP3 do?
causes release of calcium from the endoplasmic reticulum
What does DAG do?
activates PKC
What are the 3 second messengers produced as a result of Gq mediated activation of PLC?
IP3
DAG
Ca
How does G-olf work?
causes an increase in cAMP which increases Na permeability–> depolarization of olfactory neurons
What system is G-t found in? Is is inhibitory or excitatory?
transducin in the retina-visual system
inhibitory
List the 6 g-protein cascades we discussed.
G-S G-C G-Q G-OLF G-T G-i
Of the 6 g-protein cascades we discussed which two decrease the amount of cAMP (inhibitory?)
G-t
G-i
Of the 6 G-protein cascades we discussed, which two increase the amount of cAMP?
G-s
G-olf
Which g-protein cascade releases internal calcium stores using IP3 as a 2nd messenger?
Gq
Which g-protein cascade increases production of cGMP?
G-c
What are the two major classes of Cholinergic receptors?
Nicotinic (2 subtypes)
Muscarinic (5 subtypes)
Where are N-1 receptors found?
skeletal muscle
Where are N-2 receptors found?
ANS
Are cholinergic muscarinic receptors excitatory or inhibitory?
depends on location
- GI Tract- excitatory (M1)
- Heart-inhibitory (M2)
What blocks the M1 receptor?
atropine
What type of g-protein is the M1 receptor in the GI tract?
Gq- uses IP3 messanger system to increase gCa and cause depolarization–>excitation
Are the nicotinic ACh-R ionotropic or metabotropic?
ionotropic
Are the muscarinic ACh-R ionotropic or metabotropic?
metabotropic
What can a lack of Norepinephrine cause?
depression
How do tricyclics work?
by blocking NE re-uptake–> elevate mood
How do MAO-Is work to treat depression?
inhibit monoamine oxidase (which breaks down NE) and thus increase NE in terminal
Are dopamine receptors ionotropic or metabotropic?
all metabotropic
What are the three catecolamines?
dopamine, epinephrine and norepinephrine (DA, E and NE)
What neurotransmitter is involved in parkinson’s disease?
dopamine decreased (death of cells in substantia nigra)
How are D-1 and D-2 receptors different?
D-1 receptors are excitatory and cause and increase in cAMP (through Gs)
D-2 receptors are inhibitory and cause a decrease in cAMP (through Gi)
How many metabotropic GPCRs for dopamine have been identified?
4
Which condition is marked by high numbers of D-4 dopamine receptors?
Schizophrenia (treated with phenthiazines like thorazine-block D-4 receptors- DA antagonist)
How is dopamine cleared from the synaptic cleft?
Na-coupled transporter (blocked by cocaine and amphetamines)
What is serotonin (5-HT) synthesized from?
tryptophan
How many 5-HT receptors have been identified?
16 (15 GPCRS, 1 Ionotropic)
What two illegal drugs cause a transient increase in 5-HT?
LSD and ectasy
What does histamine control?
wakefulness, arousal
What are the 2 main excitatory amino acid NTs in the brain?
glutamate and aspartate
What are the 2 main inhibitory amino acid NTs in the brain?
GABA and Glycine
What are the two opoid peptides?
endorphin and enkephalin
What are the 2 ionotropic receptors for glutamate?
NMDA, AMPA, kainate
Why is the gating of the glutamatergic NMDA receptor unusual?
it is both ligand and voltage gated (Mg stuck in channel-removed above -60mV)
What is the major inhibitory NT in the brain?
GABA
What are the two type of GABA receptors?
GABA-A and GABA-B
How do GABA-A receptors function?
ionotropic receptor that increases gCl which opposes depolarization and results in inhibition
How do GABA-B receptors function?
metabotropic receptors that act through the Gi mechanism to decrease cAMP, gCa and cause inhibition
How do barbiturates and benzodiazepines such as valium work?
enhancing the effects of GABA on gCl
ie. enhanced inhibitiion
How does glycine work?
increases gCl–>inhibitory–> mostly works in the spinal cord
What is familial startle disease caused by?
mutated glycine receptor
What does strychnine block?
glycine channels- sometimes used by professional athletes to boost performance
What is vasopressin aka?
anti diuretic hormone
What is substance P most commonly involved in?
pain responsivity though recently implicated in some case of depression
What are the gas nts?
NO and CO
What does NO cause?
vasodilation of vascular smooth muscle (G-c pathway)
What do NO and CO activate?
guanylate cyclase- Gc pathway
How do ATP and adenosine act as NTs?
inhibitory NTs in the ANS
What does viagra inhibit?
PDE- Phosphodiesterase- which breaks down cAMP and cGMP
