PNS Flashcards
What is synaptobrevin anchored by?
Hydrophobic carboxy terminus
How many alpha-helices does SNAP-25 have?
2
What does AChE bind to in the basement membrane?
Collagenous tail which binds to heparan sulphate proteiglycan
What are catecholamine metabolised by?
MAO and COMT
What are the two metabolites of catecholamines?
VMA and MOPEG
Where is VMA produced?
Periphery
Where is MOPEG produced?
In CNS
Where is MAO found?
Outer membrane of mitochondria in NA nerves, liver and intestinal epithelium
How does MAO act?
Oxidative deamination to aldehyde and then aldehyde dehydrogenase to carboxylic acid
Where is COMT found?
Cytosol of liver and adrenal medulla
How does COMT act?
Methylates an aromatic hdroxyl in the catecholamine
Neurotransmitters in the vas deferens?
ATP and NA
Neurotransmitters in the bladder?
ATP and ACh
Where are P2X receptors found?
CNS and PNS
What do P2X receptors cause in non-neuronal cells?
IL1B release
What are P2X receptors selective to?
Non-selective cation
How many isoforms assemble as homo/heterotrimer in the P2X receptor?
7
What are TM1 and TM2 loops separated by in the P2X receptor?
10 disulphide bonds
Which autoreceptors does caffeine inhibit?
A1 autoreceptor
Where does the ATP bind in the P2X receptor?
Between two subunits
What are the three kinds of NOS?
Neuronal, inducible and endothelial
When is inducible NOS used?
In macrophages after LPS or IFN-gamma
What does NOS acting on L-arginine produce?
NO and L-citrulline
What mediates shear-stress?
PKB
How does cortisol affect PNMT expression?
Decreases it
What is ratio of NA:ATP storage?
4:1
How do presynaptic alpha2 receptors decrease NA release?
GPCR to K+ channel to hyperpolarise
How do presynaptic beta2 receptors enhance NA release?
Increase cAMP, increase PKA, increase calcium
What does uptake 1?
NET
What does uptake 2?
ENT
Is NET or ENT Na-dependent?
NET
How does M1 produce slow EPSP?
Inhibits K+ M current
Which family of K+ channels mediates the M current?
Kv7
Where is M2 expressed?
Presynaptically - inhibits release
WHat does alpha subunit of M2/4 do?
Inhibits adenyl cyclase
What does beta-gamma subunit of M2/4 do?
Opens GIRK channel in pacemaker tisssue
Where is M3 found?
Exocrine glands, sweat glands, oxyntic cells, smooth muscle
What does the VAT export and import?
One NA/ACh in, two H+ out
Which mAChRs act on the CNS?
4 and 5
Are P2X and P2Y ligand gated or GPCR?
P2X = ligand gated, P2Y = GPCR
What is the function of MAO?
Inactivates monoamines from gut
Which catecholamines does MAO-A work on?
Serotonin, NA and DA
Which catecholamines does MAO-B work on?
DA2
Which mAChRs are Gq coupled?
1,3,5
Which mAChRs are Gi coupled?
2 and 4
Which mAChRs are found in the PNS?
1,2,3
Which mAChRs are found in the CNS?
4 and 5
Where is M2 expressed?
Heart and nerve terminals
How does M3 cause eNOS stimulation?
Ca2+ - CaM - eNOS
Which mAChRs produce IP3 and DAG for smooth muscle and secretion?
1 and 5
What is the rate limiting step in adrenaline production?
Tyrosine to DOPA
What is chain from tyrosine to adrenaline?
Tyrosine to DOPA to dopamine to NA to adrenaline
What converts tyrosine to DOPA?
Tyrosine hydroxylase
What converts DOPA to dopamine?
DOPA decarboxylase
What converts dopamine to NA?
Dopamine beta-hydroxylase
What converts NA to adrenaline?
PNMT
Where is parasympathetic ACh instead of NA?
Sweat glands
What does retrograde axonal transport?
Dynein
What does fast axonal transport?
Kinesin
What provides electrochemical gradient for transmitters?
Proton pump acidifies vesicle interior
Which snare doe botulinum cleave?
t-SNARE
What does bungarotoxin have to degreade active zone lipids?
PLA2
Which subunits does Nneuronal have?
ALpha beta
What groups does mAChR antagonists have?
Ester, basic and aromatic replacing the acetate
What is the only uncharged stigmine?
Rivastigmine
When is VMA increased in urine?
Pheochromocytoma
Which receptor causes insulin release inhibition?
ALpha 2
Which receptor causes lipolysis and thermogenesis?
Beta 3
Which receptor causes hepatic glycogenolysis?
Beta 2
Why does NA cause vasoconstriction?
No vasodilation form beta 2
What kind of receptors are the A adenosine receptor?
All GPCRs
Two kinds of adenosine receptor?
A and P2
Which transporter takes ATP into vesciles?
VNUT
What breaks down ATP?
Ectonucleotidase
What hydrolyses ATP to inosine?
Adenosine deaminase
Why is adenosine produced during hypoxia?
Saves energy by inhibiting myocardial contractility
WHich adenosine receptors inhibit neurotransmitter release?
A1 autoreceptors
What inhibits the A1 autoreceptors?
Caffeine
What promotes expression of neuronal NOS?
Insulin
What stimulates inducible NOS in macrophages?
LPS or IFNgamma
Why does NO have no receptors?
Diffuses
How does NO activate sGC?
Interacts with its haem group
What does sGC do?
Activates PKG and relaxes smooth muscle
What does inhibitng NO do to vascular smooth muscle?
Hyperpolarises
What mediates shear-stress?
PKB
Where are nitretergic synapses found?
Upper airways, GI tract, sexual organs
Why do neuropeptides need increased calcium?
Don’t cluster at the active zone
Whcih EPSP do neuropeptides account for?
Late slow
Why can dopamine beta-hydroxylase measure sympathetic activity?
Released with NA and not degraded
What metabolises tyramine?
MAO
How does weak base affect amine packaging?
Reduces pH gradient
What is tachyphylaxis?
Need NA in vesicles to get a respose from some drugs so get less of a response after a while
How does alpha-2 decrease NA release?
GPCR to K+ channel to hyperpol
How does beta-2 enhance NA release?
Increased cAMP to increased PKA to inreased Ca2+
How do M2 receptors and delta opioid receptors affect NA release?
Both decrease
Which uptake terminates transmitter action?
Uptake 1
What is affinity and capacity of uptake 2 like?
Low affinity, high capacity
Is NET Na dependent or independent?
Dependent
Where are M1 receptors?
Smooth muscle contraction and secretion from glands
What is the rate limiting step for ACh?
Choline uptake
What is affinity of choline transporter?
High
Which is L dopa and which is carbidopa?
L-dopa can cross BBB, carbidopa can’t
What is alpha-methyl NA affinity?
Less on alpha1, same on alpha2
What is alpha1 receptor coupled to?
Gq
What is alpha2 receptor coupled to?
Gi
Which BOTOX targets synaptobrevin?
B, D, F, G
Which BOTOX targets SNAP-25 and syntaxin?
C1
What are all beta receptors coupled to?
Gs
What does malathion treat?
Head lice
What takes up adenosine?
Adenosine transporter
Which study showed G proteins have persistent signal even when internalised?
Calebiro et al 2010
Which study said alpha1 receptor has action in nicotine addiction?
Forget et al 2010
