Adrenergics Flashcards
(113 cards)
Autonomic Adrenergic Transmission
SNS Postganglionic fibers release
norepinephrine (NE) (sometimes Epi and dopamine/DA)
Catecholamine Synthesis
dopamine neurons
1) adrenergic neurons uptake L-tyrosine (blood)
2) L-tyrosine→L-dopa
(tyrosine hydroxylase/TH)
3) L-dopa→dopamine
(dopa decarboxylase/DD/l-amino acid decarboxylase)
4) dopamine into storage granules (vesicles) via active transport carrier.
5) can be released from dopamine neurons.
the rate-limiting step in synthesis
L-tyrosine→L-dopa
(by tyrosine hydroxylase/TH)
Where is phenylethanolamine n-methyltransferase (PNMT) found?
cytoplasm
Catecholamine Synthesis
Norepi neurons
NE neurons:
1) dopamine β-hydroxylase (DBH) is in the vesicles.
2) dopamine→norepi
(DBH)
3) cytoplasmic norepi (reuptake/internal release from vesicles)
↓
epinephrine
(phenylethanolamine n-methyltransferase (PNMT)
Dopa decarboxylase
specificity
what can it convert?
fairly non-selective (broad substrate specificity)
L dopa→DA
5-hydroxytryptophan→5-hydroxytryptamine
αmethyldopa→αmethyldopamine
false transmitters
α-methylnorepinephrine
α-methyldopa
Dopa decarboxylase converts α-methyldopa to α-methyldopamine, which can be further converted to….
α-methylnorepinephrine (false transmitter)
acts in feedback loop on the enzymes TH and DD to decrease excessive production
Cytoplasmic NE
if there is excessive NE release, there is (more/less) NE in the cytoplasm, thus (more/less) feedback, and (more/less) rapid synthesis
excessive NE release
less NE in cytoplasm
less feedback
more rapid synthesis
main contributor to the NE pool
NE re-uptake
the NE pools
two cytoplasmic pools
(rapid & slow turnover)
cytoplasm (ie renal medulla chromaffin cells)
In the cytoplasm, NE acts to feedback on ___ production
DA
NE in the ________ is converted to EPI before packaging in vesicles
cytoplasm of the adrenal medulla chromaffin cells
In the chromaffin cells, both EPI and NE are stored and released in the ratio of ….
80% EPI, 20% NE
important d/t receptor specificity differences between EPI and NE
Epi vs NE
which has longer doA?
Epi
Catecholamine storage is mainly in ___
granular vesicles
making granular vesicles
in cell body & carried to terminal for filling
endocytosis (pinching off) of the nerve terminal membrane.
NE in the granules is in a complex with…
-ATP (4NE:1ATP)
-proteins (NTs & neuromodulators)
-DBH/dopamine β-hydroxylase
-DA
Neuropeptide Y
protein** stored with NE**
released with NE as a co-transmitter
potent local vasoconstrictor
increases fat deposition
Two cytoplasmic pools of NE
fast and slow turnover pools
fast:
used as transmitter
stored or released directly from cytoplasm
slow:
reserve pool
use when NE too low
Adrenergic enzyme inhibitors
experimental determination of the system mechanics
α-methyl-p-tyrosine
(inhibits TH, α-methyldopa, which inhibits DD)
Disulfiram (Antabuse)
(inhibits DBH)
post synaptic receptors
A1
A2 (also pre-synpatic)
B1
B2
B3
Presynaptic A2
control mechanism to prevent overrelease
sense too much/enough NT in synapse
once stimulated, shuts off further release
