Intro | Synthesis | Release | Binding | Inactivation | Reuptake
Part 1: Image-Mapped Tutorial
Part 2: Matching Self-Test
Part 3: Multiple-Choice Self-Test
Synthesis - First, the neurotransmitter must be synthesized in the soma. These molecules are then packaged in vesicles and transported down the axon for storage in the presynaptic terminal buttons.
Release - Second, when an action potential reaches the presynaptic membrane, the neurotransmitters are released into the synaptic cleft. The amount of neurotransmitter released will depend on the rate at which action potentials reach the presynaptic membrane.
Binding - Third, released neurotransmitters will bind with the appropriate receptor sites on the postsynaptic membrane.
Inactivation - Fourth, the neurotransmitters will be inactivated by enzymes or passively removed from the synaptic cleft.
Reuptake - Fifth, some neurotransmitters will be reabsorbed by the presynaptic neuron for storage and reuse.
| Advanced |
Neurotransmitters do not usually linger at the postsynaptic membrane for long. Some of the primary neurotransmitters have been distinguished by the method used for their inactivation. The biogenic amines (serotonin and the catecholamines - norepinephrine, epinephrine, and dopamine) detach from the receptor and are either reabsorbed by the presynaptic neuron for reuse or are converted into inactive molecules by enzymes such as COMT (catechol-o-methyltransferase) and MAO (monoamine oxidase). Some anti-depressant drugs act by inhibiting MAO and, therefore, increase the active form of these neurotransmitters. Acetylcholine is inactivated by the enzyme acetylcholinesterase after it is released from the receptor. This enzyme breaks the molecule down in acetyl and choline fragments; neither of these molecules are effective at stimulating the receptor. The choline fragment is reabsorbed by the presynaptic neuron and recycled. In the absence of the breakdown enzyme, acetylcholine excitation of the postsynaptic membrane may be prolonged. This mechanism is used to treat the condition called myasthenia gravis, which is characterized by reduced acetylcholine synaptic transmission. Drugs that block acetylcholinesterase may alleviate the symptoms associated with inadequate acetylcholine activity.
The various classes of drugs such as stimulants, opiates, and hallucinogens exert their effects by intervening at any one or more of the stages involved in synaptic transmission. The stimulant drugs such as amphetamine and cocaine generally increase activity and sensory arousal. They also intensify feelings of contentment and pleasure. Amphetamine stimulates dopamine activity by stimulating its release from the presynaptic neuron and by blocking reuptake by the presynaptic neuron. Cocaine blocks the reuptake of both norepinephrine and dopamine. Cocaine has a dose-dependent response. At low dosages, it stimulates D2 receptors, which are excitatory, while at higher doses it stimulates D1 receptors, which are inhibitory. The opiate drugs induce euphoria and decrease pain. They include opium, heroin, morphine, and methadone.
The opiates affect endorphin activity because they resemble the endogenous neuromodulators (agonist effects) in the brain causing the following chain reaction: endorphin activation inhibits GABA release. This GABA release inhibits dopamine release. The hallucinogenic drugs such as lysergic acid diethylamide (LSD), phencyclidine (PCP), and mescaline are also agonists, resembling the neurotransmitter serotonin (5-HT). Agonists bind to the receptor site in place of the natural neurotransmitter or modulator, and thereby increase activity of serotonin. This increased serotonin activity results in a dream-like state and vivid perceptions that have no basis in reality. LSD has a selective effect on only one of several serotonin receptors, 5-HT2. When LSD binds to this widespread receptor, it blocks normal serotonin stimulation. How this leads to the development of hallucinations has not yet been determined.
| Suggestions for further study |
Dunant, Y., Israel, M. (1985, April). The release of acetylcholine, Scientific American, 252(4), 58-66.
Gottlieb, D.I. (1988, February). GABAergic neurons, Scientific American, 258(2), 82-89.
Holloway, M. (1991, March). Rx for addiction, Scientific American, 264(3), 94-103.
Iverson, L.L. (1979, September). The chemistry of the brain. Scientific American, 241(3), 134-144.
Lester, H.A. (1977, February). The response to acetylcholine. Scientific American, 236(2), 106-116, 118.
Nathanson, J.A., Greengard, P. (1977, August). "Second messengers" in the brain, Scientific American, 237(2), 109-119.
Snyder, S.H. (1977, March). Opiate receptors and internal opiates, Scientific American, 236(3), 44-56.
Snyder, S.H., Bredt, D.S. (1992, May). Biological roles of nitric oxide, Scientific American, 266(5), 68-71, 74-77.
Van Heyningen, W.E. (1968, April). Tetanus, Scientific American, 218(4), 69-73.
Wurtman, R.J. (!982, April). Nutrients that modify brain function, Scientific American, 246(4), 50-59.
Zivin, J.A. Choi, D.W. (1991, July). Stroke therapy, Scientific American, 265(1), 56-63.
http://www.sfn.org/briefings/nmda.html
(NMDA Receptors)
from Society for Neuroscience - Brain Briefings, 1994.
NMDA receptor blockers and the prevention of neuronal damage due to
stroke, epilepsy, Huntington's Disease, and AIDS.