UNIVERSITY OF THE SOUTHERN CARIBBEAN

MARACAS ROYAL ROAD, MARACAS, ST. JOSEPH.

Assignment 3

An Assignment
Presented in Partial Fulfilment
Of the Requirements of this Course
BIOL420 PHARMACOLOGY

INSTRUCTOR: Dr. Arlene Williams

By
Jamela Wallace

20th OCT-2014

Approval ..

1. There are three major neurotransmitters involved in the PNS what are they called?
a) acetylcholine b) norepinephrine c) epinephrine
Acetylcholine: an excitatory neurotransmitter that is a derivative of the amine, choline; the
transmitter is released by motor neurons at the neuromuscular junction, by all preganglionic
autonomic visceral motor neurons, by all parasympathetic postganglionic visceral motor neurons,
by sympathetic postganglionic visceral motor neurons for sweat glands, and by a variety of
neurons in the CNS. This neurotransmitter is rapidly cleared from synapses by the enzyme
acetylcholinesterase.
Norepinephrine (noradrenaline): is a catecholamine, both a hormone and
neurotransmitter; it may be excitatory or inhibitory, depending on its target
cell's response; the transmitter released by the adrenal medulla and by
practically all postganglionic neurons of the sympathetic nervous system
(except the postganglionic neurons that go to sweat glands) to cause
vasoconstriction and increases in heart rate, blood pressure, and the glucose
level of the blood; this neurotransmitter is rapidly cleared from synapses by
the enzymes catechol-o-methyl-transferase (COMT) and monoamine oxidase
(MAO)
Epinephrine: is a sympathomimetic drug that activates an adrenergic receptive mechanism on
effector cells and imitates all actions of the sympathetic nervous system, except those on the
arteries of the face and sweat glands. Epinephrine acts on both alpha and beta receptors and is the
most potent alpha receptor activator. This neurotransmitter is released by the adrenal medulla.

2. Outline the synthesis of epinephrine (Arenaline)

3. Discuss the events that take place at the sympathetic neroeffector junction and at the preand post-synaptic clefts
Exocytosis occurs at specialized locations on sympathetic varicosities dictated by the
cell-surface expression of specialized docking proteins that interact with other proteins on
the surfaces of secretory vesicles. The process is stimulated by an influx of Ca2+, which in
neurons is controlled primarily by nerve impulsemediated membrane depolarization,

and in adrenal medullary cells by acetylcholine release from innervating splanchnic

nerves. The wide range of voltage-, receptor-, G protein, and second messenger
operated Ca2+ channels provide numerous points for regulation of Ca2+-triggered
exocytosis. In this way, a variety of peptides, neurotransmitters, and humoral factors
provide additional mechanisms for stimulation of exocytosis or may act to modulate
nerve impulsestimulated release of catecholamines. Norepinephrine also inhibits its own
release through occupation of presynaptic 2-adrenoceptors.
Because the enzymes responsible for the metabolism of catecholamines have intracellular
locations, the primary mechanism limiting the life span of catecholamines in the
extracellular space is uptake by active transport, not metabolism by enzymes.Uptake is
facilitated by transporters that belong to two families with mainly neuronal and
extraneuronal locations. The neuronal norepinephrine transporter provides the principal
mechanism for rapid termination of the signal in sympathoneuronal transmission,
whereas transporters at extraneuronal locations are more important for limiting the spread
of the signal and for clearing catecholamines from the bloodstream.

4. Define catecholamines and how they are released

Catecholamines are a group of neurotransmitters that share two chemical similarities. They have
one core structure of catechol and an amine group. They are sympathomimetic "fight-or-flight"
hormones that are released by the adrenal glands in response to stress.

Once catecholamines have been synthesized, Catecholaminergic neurons use a vesiclular

monoamine transporter (VMAT) to transport the neurotransmitter molecules from the cytoplasm
of the cell to the interior of the synaptic vesicles. This vesicular packaging provides a means for
releasing a predertermined amount neurotransmitter (several thousand molecules per vesicle), as
well as protects the neurotransmitter from degradation by enzymes within the nerve terminal.
When a nerve impulse enters the terminal it triggers the entry of Ca2+, which results in the
exocytosis of the catecholamines and ATP, some neuroactive peptides or their precursors.
Interaction of molecular proteins induces the docking of the granules at the plasma membrane
which leads to the secretion of one or more vesicles that release their contents into the synaptic
cleft.

5. Describe what happens to catecholamines after they are released (their mechanism)
After their release from sympathetic terminals, all neurotransmitters can feedback on
prejunctional receptors to inhibit the subsequent exocytosis. Autoreceptors located on the cell
bodies, terminals, and dentrites of dopaminergic and noradrenergic neurons inhibit the release of
catecholamines by reducing the rate of firing of the cell. The neurotransmitter molecules are
either returned to the terminal through transporters, re-packaged into the vesicles for re-release or
the remainder are broken down and eliminated
Reuptake of catecholamines including NE into (postganglionic) sympathetic nerve terminals is
facilitated by an amine uptake pump. This pump is driven indirectly by a sodium gradient, which
is in turn generated by another plasma membrane protein, the Na+,K+-ATPase, or sodium,
potassium pump. The amine uptake pump is selective for NE and to a lesser extent Epi, but it
does not take up isoproterenol. Catecholamines which diffuse into the circulation or are released
as neurohormones may also be taken up into sympathetic nerve terminals.
For norepinephrine released by sympathetic nerves, about 90% is removed back into nerves by
neuronal uptake, 5% is removed by extraneuronal uptake, and 5% escapes these processes to
enter the bloodstream. In contrast, for epinephrine released directly into the bloodstream from
the adrenals, about 90% is removed by extraneuronal monoamine transport processes, the liver
being particularly important. The presence of these highly active transport processes means that
catecholamines are rapidly cleared from the bloodstream with a circulatory half-life of less than
2 minutes.

6. What are the roles of catecholamines

Catecholamines (1) act as neuromodulators in the central nervous system and (2) as hormones in
the blood circulation. (3) They also cause physiological changes that prepare the body for the

"fight-or-flight" response. This includes: increased heart rate, blood pressure, breathing rate,
muscle strength and mental alertness. They also reduce the amount of blood going to the skin and
increase blood flow to the major organs, such as the brain, heart and kidneys.

7. Define adrenergic drug and cholinergic drugs

Adrenergic drugs closely resemble the neurotransmitter norepinephrine which acts directly on
adrenergic receptors. Thus, adrenergic drugs act to stimulate the adrenergic nerves directly by
mimicking the action of norepinephrine or indirectly by stimulating the release of
norepinephrine. Effects include: increased blood pressure, constricting blood vessels, opening
the airways leading to the lungs and increased heart rate.
Similarly cholinergic drugs closely resemble the neurotransmitter acetylcholine, the primary
transmitter of nerve impulses within the parasympathetic nervous system. These drugs inhibit,
enhance, or mimic the action of acetylcholine causing contraction of smooth muscles, dilated
blood vessels, increased bodily secretions, and a slowed the heart rate.

8. What is Amphetamine and how is it related to the sympatheitic nervous system

Amphetamines are a group of synthetic psychoactive drugs called central nervous system (CNS)
stimulants. Amphetamines also stimulate the sympathetic division of the peripheral nervous
system. When used, the neurotransmitters dopamine and norepinephrine are released from nerve
endings in the brain and their reuptake is inhibited. This influx causes the buildup of
neurotransmitters at synapses in the brain. When nerve cells in the brain and spinal cord are
activated by amphetamine, the mental focus, the ability to stay awake, and the ability to
concentrate is improved.
9. Phenoxybenzamine is an alpha-receptor blocker outline its mechanism of action at the
synapse
Phenoxybenzamine links covalently to both 1-postsynaptic and 2-presynaptic receptors. The
block is irreversible and noncompetitive. Thus, the body can overcome the block by synthesizing
new adrenoceptors, which requires a day or more. Therefore, the actions of phenoxybenzamine
last about 24 hours after a single administration. The blocking receptors, result in (1) more
norepinephrine release (In the heart, this stimulates receptors on the heart to increase cardiac
output (high B.P)). (2) as an -adrenergic blocker it reverses the -agonist actions such as
epinephrine. (3) diminishes NE actions

10. What are re-uptake inhibitors and what is their purpose in neurotransmission?
Neurotransmitters can sometimes undergo reuptake too quickly, or at reduced production and this
can cause neurochemical imbalances. A type of medication called a reuptake inhibitor or
transporter blocker prevents the reuptake of specific neurotransmitters by the pre-synaptic
plasmellama amine transport proteins. It this way it prolongs the effect of the neurotransmitter
allowing more of a neurotransmitter to be available to the post synapse. Selective Serotonin
Reuptake Inhibitors (SSRIs) is an example of one of these medications. SSRIs potentiate and
prolong the action of 5-HT (serotonin) released by neuronal activity.
Other reuptake inhibitors: Sibutramine, Reboxetine and cocaine