Exam #02 (General Info) Flashcards
Major peripheral effects for alpha-1 receptor
vasoconstriction, mydriasis (constricting the muscle dilates the pupil)
Major peripheral effects for alpha-2 receptor
inhibit ACh, NE release (this inhibits sympathetic tone)
Major peripheral effects for beta-1 receptor
stimulate HR and force of contraction
Major peripheral effects for beta-2 receptor
relax respiratory, uterine, vascular skeletal muscle, stimulate glycogenolysis and insulin release
Major peripheral effects for beta-3 receptor
stimulate lipolysis
Major peripheral effects for D-1 receptor
dilation of renal blood vessels
Synthesis pathway and release of NE at adrenergic synaptic junction
- Tyrosine cotransported into cell with Na+
- Tyrosine hydroxylase converts tyrosine to L-DOPA (rate-limiting step)
- Dopa decarboxylase converts L-DOPA to DA
- DA is transported into vesicle via VMAT (this would be the last step if this was a dopaminergic neuron)
- DA hydroxylase converts DA into NE in the vesicle
- AP traveling down the neuron, opens Ca+2 channels
- Ca+2 causes vesicle to bind to presynaptic membrane and dump NE into synaptic cleft
Fate of NE once dumped in synaptic cleft
- It can bind to adrenergic 7TM-GPCR (alpha or beta)
- it is metabolized by MAO and COMT
- transported back into the neuron via NET (reuptake)
- bind to autoreceptor
NE Autoreceptor mechanism (include autoreceptor type)
Major negative feedback mechanism for NE. Autoreceptor is an alpha-2 receptor. NE binding to autoreceptor reduces NE release. NE is an agonist at the auto receptor, but has indirect antagonistic effects
Main way NE is cleared from synaptic cleft
reuptake via NET
2 drugs that block the NET and the effects it causes
cocaine and tricyclic-antidepressants
these drugs block the NET increasing NE conc. in synaptic cleft thereby increasing NE activity
So, these drugs are acting like indirect agonists
Heteroceptor
binds different NT than one being released. Helps regulate the NT being released
% of NE and Epi stored within the adrenal medulla
80% Epi
20% NE
Where in adrenal medulla Epi and NE are stored
chromaffin granules (similar to vesicles)
Where is NE methylated to form Epi?
in the cytoplasm
Would NE released from adrenal medulla into blood be considered a NT or hormone?
hormone
The rate of synthesis (NE –> Epi) is tightly tied to what steroid hormones secreted by the adrenal cortex?
glucocorticoids
Stimulation of alpha-1 receptor by catecholamines leads to the activation of what G-protein?
Gq coupling protein
Describe what the Gq protein goes on to activate once stimulated by binding of catecholamine to alpha-1 receptor and the 2nd messengers involved
the activated alpha-q subunit of the G-protein goes on to activate Phospholipase C which leads to the release of IP3 and DAG
What function do the 2nd messengers released from alpha-1 receptor activation from catecholamine binding?
- IP3 stimulates release of sequestered Ca+2 increasing cytoplasmic [Ca+2] which may activate Ca+2 dependent protein kinases
- DAG activates protein kinase C (PKC)
Binding of catecholamines to beta receptors leads to the activation of what G-protein?
Gs (stimulatory G-protein)
Binding of catecholamines to alpha-2 receptor leads to the activation of what G-protein?
Gi (inhibitory G-protein
Explain the cascade of events after activation of Gs?
- Activation of Gs leads to dissociation of the G-protein’s alpha subunit charged with GTP
- GTP-alpha subunit directly activates adenylyl cyclase which INCREASES [cAMP]
Explain the cascade of events after activation of Gi?
- Activation of Gi leads to dissociation of the G-protein’s alpha-i subunit charged with GTP
- GTP-alpha-i subunit inhibits adenylyl cyclase which DECREASES [cAMP]
