|
Pharmacology => Drug => Neurotransmitter
Neurotransmitter
INTRODUCTION
Neurotransmitter, chemical made by neurons, or nerve cells. Neurons send out neurotransmitters as chemical signals to activate or inhibit the function of neighboring cells.
Within the central nervous system, which consists of the brain and the spinal cord, neurotransmitters pass from neuron to neuron. In the peripheral nervous system, which is made up of the nerves that run from the central nervous system to the rest of the body, the chemical signals pass between a neuron and an adjacent muscle or gland cell.
TYPES OF NEUROTRANSMITTERS
Nine chemical compounds-belonging to three chemical families-are widely recognized as neurotransmitters. In addition, certain other body chemicals, including adenosine, histamine, enkephalins, endorphins, and epinephrine, have neurotransmitterlike properties. Experts believe that there are many more neurotransmitters as yet undiscovered.
The first of the three families is composed of amines, a group of compounds containing molecules of carbon, hydrogen, and nitrogen. Among the amine neurotransmitters are acetylcholine, norepinephrine, dopamine, and serotonin. Acetylcholine is the most widely used neurotransmitter in the body, and neurons that leave the central nervous system (for example, those running to skeletal muscle) use acetylcholine as their neurotransmitter; neurons that run to the heart, blood vessels, and other organs may use acetylcholine or norepinephrine. Dopamine is involved in the movement of muscles, and it controls the secretion of the pituitary hormone prolactin, which triggers milk production in nursing mothers.
The second neurotransmitter family is composed of amino acids, organic compounds containing both an amino group (NH2) and a carboxylic acid group (COOH). Amino acids that serve as neurotransmitters include glycine, glutamic and aspartic acids, and gamma-amino butyric acid (GABA). Glutamic acid and GABA are the most abundant neurotransmitters within the central nervous system, and especially in the cerebral cortex, which is largely responsible for such higher brain functions as thought and interpreting sensations.
The third neurotransmitter family is composed of peptides, which are compounds that contain at least 2, and sometimes as many as 100 amino acids. Peptide neurotransmitters are poorly understood, but scientists know that the peptide neurotransmitter called substance P influences the sensation of pain.
In general, each neuron uses only a single compound as its neurotransmitter. However, some neurons outside the central nervous system are able to release both an amine and a peptide neurotransmitter.
Neurotransmitters are manufactured from precursor compounds like amino acids, glucose, and the dietary amine called choline. Neurons modify the structure of these precursor compounds in a series of reactions with enzymes. Neurotransmitters that come from amino acids include serotonin, which is derived from tryptophan; dopamine and norepinephrine, which are derived from tyrosine; and glycine, which is derived from threonine. Among the neurotransmitters made from glucose are glutamate, aspartate, and GABA. Choline serves as the precursor for acetylcholine.
HOW NEUROTRANSMITTERS WORK
Neurotransmitters are released into a microscopic gap, called a synapse, that separates the transmitting neuron from the cell receiving the chemical signal. The cell that generates the signal is called the presynaptic cell, while the receiving cell is termed the postsynaptic cell.
After their release into the synapse, neurotransmitters combine chemically with highly specific protein molecules, termed receptors, that are embedded in the surface membranes of the postsynaptic cell. When this combination occurs, the voltage, or electrical force, of the postsynaptic cell is either increased (excited) or decreased (inhibited).
When a neuron is in its resting state, its voltage is about -70 millivolts. An excitatory neurotransmitter alters the membrane of the postsynaptic neuron, making it possible for ions (electrically charged molecules) to move back and forth across the neuron's membranes. This flow of ions makes the neuron's voltage rise toward zero. If enough excitatory receptors have been activated, the postsynaptic neuron responds by firing, generating a nerve impulse that causes its own neurotransmitter to be released into the next synapse. An inhibitory neurotransmitter causes different ions to pass back and forth across the postsynaptic neuron's membrane, lowering the nerve cell's voltage to -80 or -90 millivolts. The drop in voltage makes it less likely that the postsynaptic cell will fire.
If the postsynaptic cell is a muscle cell rather than a neuron, an excitatory neurotransmitter will cause the muscle to contract. If the postsynaptic cell is a gland cell, an excitatory neurotransmitter will cause the cell to secrete its contents.
While most neurotransmitters interact with their receptors to create new electrical nerve impulses that energize or inhibit the adjoining cell, some neurotransmitter interactions do not generate or suppress nerve impulses. Instead, they interact with a second type of receptor that changes the internal chemistry of the postsynaptic cell by either causing or blocking the formation of chemicals called second messenger molecules. These second messengers regulate the postsynaptic cell's biochemical processes and enable it to conduct the maintenance necessary to continue synthesizing neurotransmitters and conducting nerve impulses. Examples of second messengers, which are formed and entirely contained within the postsynaptic cell, include cyclic adenosine monophosphate, diacylglycerol, and inositol phosphates.
Once neurotransmitters have been secreted into synapses and have passed on their chemical signals, the presynaptic neuron clears the synapse of neurotransmitter molecules. For example, acetylcholine is broken down by the enzyme acetylcholinesterase into choline and acetate. Neurotransmitters like dopamine, serotonin, and GABA are removed by a physical process called reuptake. In reuptake, a protein in the presynaptic membrane acts as a sort of sponge, causing the neurotransmitters to reenter the presynaptic neuron, where they can be broken down by enzymes or repackaged for reuse.
IVROLES OF NEUROTRANSMITTERS IN DISEASE Neurotransmitters are known to be involved in a number of disorders, including Alzheimer's disease. Victims of Alzheimer's disease suffer from loss of intellectual capacity, disintegration of personality, mental confusion, hallucinations, and aggressive-even violent-behavior. These symptoms are the result of progressive degeneration in many types of neurons in the brain. Forgetfulness, one of the earliest symptoms of Alzheimer's disease, is partly caused by the destruction of neurons that normally release the neurotransmitter acetylcholine. Medications that increase brain levels of acetylcholine have helped restore short-term memory and reduce mood swings in some Alzheimer's patients.
Neurotransmitters also play a role in Parkinson's disease, which slowly attacks the nervous system, causing symptoms that worsen over time. Fatigue, mental confusion, a masklike facial expression, stooping posture, shuffling gait, and problems with eating and speaking are among the difficulties suffered by Parkinson's victims. These symptoms have been partly linked to the deterioration and eventual death of neurons that run from the base of the brain to the basal ganglia, a collection of nerve cells that manufacture the neurotransmitter dopamine. The reasons why such neurons die are yet to be understood, but the related symptoms can be alleviated. L-dopa, or levodopa, widely used to treat Parkinson's disease, acts as a supplementary precursor for dopamine. It causes the surviving neurons in the basal ganglia to increase their production of dopamine, thereby compensating to some extent for the disabled neurons.
Many other effective drugs have been shown to act by influencing neurotransmitter behavior. Some drugs work by interfering with the interactions between neurotransmitters and intestinal receptors. For example, belladonna decreases intestinal cramps in such disorders as irritable bowel syndrome by blocking acetylcholine from combining with receptors. This process reduces nerve signals to the bowel wall, which prevents painful spasms.
Other drugs block the reuptake process. One well-known example is the drug fluoxetine (Prozac), which blocks the reuptake of serotonin. Serotonin then remains in the synapse for a longer time, and its ability to act as a signal is prolonged, which contributes to the relief of depression and the control of obsessive-compulsive behaviors.
Back
|
