UNIVERSITY OF THE SOUTHERN CARIBBEANMARACAS ROYAL ROAD, MARACAS, ST. JOSEPH.

Assignment 3

An Assignment Presented in Partial FulfilmentOf the Requirements of this CourseBIOL420 PHARMACOLOGY

INSTRUCTOR: Dr. Arlene Williams

ByJamela 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 pre-and post-synaptic cleftsExocytosis 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 messengeroperated 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 eliminatedReuptake 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 catecholaminesCatecholamines (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 drugsAdrenergic 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 systemAmphetamines 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 synapsePhenoxybenzamine 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