| • important regulator of virtually all organ systems
• crucial for the maintenance of blood pressure even
under relatively minor situations of stress (e.g.
gravitational stress of standing)
• mediated by the release of NE from nerve terminals,
which then activates postsynaptic sites
• adrenal medulla releases Epi, in response to stimuli
(stress) | SYMPATHETIC NERVOUS SYSTEM |
| 1 Epinephrine acts as __
2 Norepinephrine acts as __ | 1 hormone
2 neurotransmitter |
| Differentiate Hormones and Neurotransmitters | HORMONES:
1 released by ENDOCRINE GLANDS
2 travel through blood to act on DISTANT TARGET CELLS
3 the effects are SLOWER but LONGER LASTING
4 part of the ENDOCRINE SYSTEM
NEUROTRANSMITTERS:
1 released by the NERVE CELLS
2 travel across the SYNPASE to act on NEARBY CELLS
3 the effects are FAST ACT but SHORTER LASTING
4 part of NERVOUS SYSTEM |
| Neurotransmission at adrenergic neurons process | 1 Tyrosine is hydroxylated into Dihydroxyphenylalanine (DOPA) by Tyrosine Hydroxylase.
It is then converted to Dopamine by Aromatic l-amino acid decarboxylase in the presynaptic neurons
2 Dopamine is transported to vesicles.
Dopamine is hydroxylated to form Norepinephrine.
3 Influx of Ca2+ causes vesicle to fuse with cell membrane and undergo EXOCYTOSIS.
4 Norepinephrine binds to Post synaptic receptor
5 Norepinephrine diffuses out of synaptic space and go to systemic circulation.
or turned inactive metabolite by catechol-O methyltransferase
or
REUPTAKE back to the Neuron
6 Methylated by COMT and oxidized by MAO |
| Inhibits the formation of DOPA from Tyrosine | Metyrosine |
| 1 Release Stimulators:
2 Release Inhibitors | 1 Tyramine, Ephedrine, Amphetamine, Angiotensin II, Latrotoxin
2 Guanethidine, Guanadrel, Bretylium |
| The carrier system that transports DOPAMINE into the synaptic vesicle is BLOCKED by __ | Reserpine |
| Drugs that BLOCK the RELEASE of Norepinephrine | Guanethidine |
| REUPTAKE of Norepinephrine can be inhibited by __ | 1 Imipramine (Tricylic Antidepressant)
2 Duloxetine
3 Cocaine
4 Reboxitin (first commercially available) |
| 1 Enzyme that degrade/metabolize Norepinephrine
2 Enzyme that Oxidizes Norepinephrine | 1 Catechol-O-methyltransferase (COMT)
2 Monoamine oxidases (MAO) |
| the principal route by which norepinephrine is
removed after its release from the synaptic cleft
removes 90% of released NE; other NE left may bind
and activate the receptors or they may enter the
bloodstream and be metabolized by COMT | Norepinephrine Transporter (NET) |
| NE taken back to cells may be
metabolized by MAO to | dihydroxyphenylglycol (DHPG) |
| drugs that mimic the actions of
epinephrine or norepinephrine | Sympathomimetic Drugs |
| • Acts DIRECTLY on alpha or beta
receptors
• Norepinephrine and Epinephrine | Direct Agonists |
| Actions are DEPENDENT on the release of
endogenous CATECHOLAMINES | Indirect Agonists |
| • Stimulate adrenoceptors directly
and release norepinephrine
• Ephedrine | Mixed-action Agonists |
| Types of Receptors | 1 Alpha Receptors
• Alpha 1
• Alpha 2
2 Beta Receptors
• Beta 1
• Beta 2
• Beta 3
3 Dopamine Receptors |
| a drug may PREFERENTIALLY bind to one subgroup of
receptors at concentrations too low to interact
extensively with another subgroup | Receptor Selectivity
EXAMPLE:
NE - Alpha 1 = Alpha 2; Beta 1 >> Beta 2
Epi - Alpha 1 = Alpha 2; Beta 1 = Beta 2 |
| 1 Alpha Receptors
2 Beta Receptors | 1 Epinephrine ≥ Norepinephrine >>
Isoproterenol
2 Isoproterenol > Epinephrine ≥
Norepinephrine |
