neurotransmitters/ Small-Molecule Transmitters

Question 1

acetylcholine

Answer 1

1. enclosed in small clear synaptic vesicles (nongranulated)
2. Acetylcholine is the acetyl ester of choline
3. Synthesis of acetylcholine involves the reaction of choline with active acetate (acetyl coenzyme A, acetyl-CoA), catalyzed by the enzyme choline acetyltransferase.
4. Acetylcholine must be rapidly removed from the synapse if repolarization is to occur. (hydrolysis of acetylcholine to choline and acetate, a reaction catalyzed by the enzyme acetylcholinesterase.)
5. Muscarine mimics the stimulatory action of acetylcholine on smooth muscle and glands. the receptors involved are muscarinic cholinergic receptors. They are blocked by the drug atropine.
6. Nicotine mimics the stimulatory effect of acetylcholine at the motor end plate of the skeletal striated muscle cells. The receptors involved are called nicotinic cholinergic receptors. This action is antagonized by substances like curare.
7. is secreted by neurons in
   many areas of the nervous system but specifically by
   (1) the terminals of the large pyramidal cells from the
   motor cortex, (2) several different types of neurons in
   the basal ganglia, (3) the motor neurons that innervate
   the skeletal muscles, (4) the preganglionic neurons of the
   the autonomic nervous system, (5) the postganglionic neurons
   of the parasympathetic nervous system, and (6) some of
   the postganglionic neurons of the sympathetic nervous
   system. In most instances, acetylcholine has an excitatory
   effect; however, it is known to have inhibitory effects at
   some peripheral parasympathetic nerve endings, such as
   inhibition of the heart by the vagus nerves.

Question 2

noradrenaline/ norepinephrine?

Answer 2

1. stored in the synaptic knobs in small vesicles (granulated vesicles).
2. Noradrenaline-secreting neurons are noradrenergic neurons
3. secreted by the terminals of many
   neurons whose cell bodies are located in the brain stem
   and hypothalamus. Specifically, norepinephrine-secreting
   neurons located in the locus ceruleus in the pons send
   nerve fibers to widespread areas of the brain to help
   control overall activity and mood of the mind, such as
   increasing the level of wakefulness. In most of these areas,
   norepinephrine probably activates excitatory receptors,
   but in a few areas, it activates inhibitory receptors instead.
   Norepinephrine is also secreted by most postganglionic
   neurons of the sympathetic nervous system, where it
   excites some organs but inhibits others.

Question 3

Dopamine

Answer 3

1. secreted by neurons that originate in the
   substantia nigra.
2. The termination of these neurons is
   mainly in the striatal region of the basal ganglia.
3. The effect of dopamine is usually inhibition.
4. There is active reuptake of dopamine and it is metabolized to inactive compounds by MAO and COMT.

Question 4

Fate of norepinephrine

Answer 4

1. Re-uptake into the presynaptic neurons
   - In the presynaptic knob, noradrenalin/norepinephrine is metabolized to biologically inactive deaminated products by oxidation, a reaction catalyzed by monoamine oxidase (MAO), an enzyme located on the outer surface of the mitochondria.
2. Removal by diffusion out of the synaptic cleft into the surrounding fluids
   - i. Part of the molecules of noradrenaline leaves the synaptic cleft and moves to the interstitial fluid.
   ii. noradrenaline is trapped by cells in which it undergoes an O-methylation, catalyzed by catechol –O-methyltransferase (COMT), an enzyme widely distributed, particularly in the liver, kidneys, and smooth muscles. In the brain, it is present in glial cells, and small amounts are found in postsynaptic neurons, but none is found in presynaptic noradrenergic neurons.
   iii. Vanillylmandelic acid (VMA), a product of oxidation of O- methylated derivatives of noradrenaline and adrenaline, is the most plentiful catecholamine metabolite in the urine.

Question 5

Alpha and beta receptor

norepinephrine and epinephrine

Answer 5

1. Adrenaline and noradrenaline both act on α and β receptors.
2. noradrenaline has a greater affinity for α adrenergic receptors.
3. adrenaline for β adrenergic receptors.
4. These α and β receptors are linked to G proteins.

Question 6

noradrenaline/ norepinephrine?

Answer 6

1. stored in the synaptic knobs in small vesicles (granulated vesicles).
2. Noradrenaline-secreting neurons are noradrenergic neurons
3. secreted by the terminals of many
   neurons whose cell bodies are located in the brain stem
   and hypothalamus. Specifically, norepinephrine-secreting
   neurons located in the locus ceruleus in the pons send
   nerve fibers to widespread areas of the brain to help
   control overall activity and mood of the mind, such as
   increasing the level of wakefulness. In most of these areas,
   norepinephrine probably activates excitatory receptors,
   but in a few areas, it activates inhibitory receptors instead.
   Norepinephrine is also secreted by most postganglionic
   neurons of the sympathetic nervous system, where it
   excites some organs but inhibits others.

Question 7

Glycine

Answer 7

1. Glycine is secreted mainly at synapses in the spinal cord.
2. It is believed to always act as an inhibitory transmitter

Question 8

GABA (gamma-aminobutyric acid)

Answer 8

GABA (gamma-aminobutyric acid) is secreted by nerve terminals in the spinal cord, cerebellum, basal ganglia, and many areas of the cortex.
2. It is believed to always cause inhibition

Question 9

Glutamate

Answer 9

1. Glutamate is secreted by the presynaptic terminals in many of the sensory pathways entering the central nervous the system, as well as in many areas of the cerebral cortex.
2. It probably always causes excitation.

Question 10

Serotonin

Answer 10

1. Serotonin is secreted by nuclei that originate in the
   median raphe of the brain stem and project to many brain and spinal cord areas, especially to the dorsal horns of the spinal cord and to the hypothalamus.
2. Serotonin acts as an inhibitor of pain pathways in the cord, and an inhibitor action in the higher regions of the nervous system is believed to help control the mood of the person, perhaps even to cause sleep.

Question 11

Nitric oxide

Answer 11

1. Nitric oxide is especially secreted by nerve terminals
   in areas of the brain responsible for long-term behavior and memory.
2. Nitric oxide is different from other small-molecule transmitters in its
   mechanism of formation in the presynaptic terminal and in its actions on the postsynaptic neuron.
3. It is not preformed and stored in vesicles in the presynaptic terminal as are other transmitters. Instead, it is synthesized almost instantly as needed and then diffuses out of the presynaptic terminals over a period of seconds rather than being released in vesicular packets.
4. it diffuses into postsynaptic neurons nearby. In the postsynaptic neuron, it usually does not greatly alter the membrane potential but instead changes intracellular metabolic functions that modify neuronal excitability for seconds, minutes, or perhaps even longer.