Receptors = cellular recognition sites. Each type of receptor binds to a specific molecule.
Ligand = a specific molecule that binds to a receptor.
Peptide = a compound consisting of two or more amino acids linked in a chain, the carboxyl group of each acid being joined to the amino group of the next by a bond of the type -OC-NH-.
The first component of the molecules of emotion is a molecule found on the surface of cells in body and brain called the opiate receptor. It was my discovery of the opiate receptor that launched my career as a bench scientist in the early 1970, when I found a way to measure it and thereby prove its existence. At that time a receptor was mostly an idea, a hypothetical site believed to be located somewhere in the cells of all living things.
The scientists who most needed to believe in it were the pharmacologists because because it was the only way they knew to explain the action of drugs in the organism. "No drug acts unless it is fixed," said Paul Ehrlich, the first modern pharmacologist, summarizing what he believed to be true, even though he had no real evidence.
Now we know that the receptor is a single molecule, perhaps the most elegant, rare, and complicated kind of molecule there is. A molecule is the tiniest possible piece of a substance that can still be identified as the substance. Each molecule of any substance is composed of the smallest units of matter --- atoms such as carbon an hydrogen and nitrogen --- which are bonded together in a configuration specific to that substance, which can be expressed as chemical formula.
Invisible forces attract one molecule to another, so that the molecules cohere into an identifiable substance. These invisible forces of attraction can be overcome if enough energy is applied to the substance. For example, heat energy will melt ice crystals, turning them into water, which will then vaporize into steam as its molecules move so fast, with so much energy, that they break loose of each other and fly apart.
But the chemical formula remains the same for each state --- in this case H2O, the two hydrogen atoms bonded to one oxygen atom --- whether that state is an icy solid, a wateryliquid, or colorless vapor.
📝A chemical formula = a molecule
The receptors are molecules, and are made up of proteins, tiny amino acids strung together in crumpled chains, looking something like beaded necklaces that have folded in on themselves.
If you were to assign a different color to each of the receptors that scientists have identified, the average cell surface would appear as a multicolored mosaic of lat least 70 different hues.
Molecular biologists can isolate these receptors, determine their molecular weight, and eventually crack their chemical structure, which means identifying the exact sequence of amino acids that makes up the receptor molecule. Their complete chemical structure can now be diagrammed.
Basically, receptors function as sensing molecules --- scanners. Just like our sense organs (eyes, ears, nose, tongue, fingers, and skin ) .
They hover in the membranes of your cells, dancing and vibrating, waiting to pick up messages carried by other vibrating little creatures, also made of amino acids --- diffusing is the technical word --- through the fluids surrounding each cell. We like to describe these receptors as "keyholes," although that is not an altogether precise term.
All receptors are proteins. They cluster in the cellular membrane waiting for the right chemical keys to swim up to them and to mount them by fitting into their keyholes --- a process known as binding.
Binding. It's sex on a molecular level.
And what is this chemical key that docks onto the receptor and causes it to dance and sway? The responsible element is called a ligand. This is the chemical key that binds to the receptor, entering it like a key in a keyhole, creating a disturbance to tickle the molecule into rearranging itself, changing its shape until --- click! --- information enters the cell.
If receptors are the first components of the molecule of emotion, the ligands are the second. The word ligand comes from the Latin ligate, "that which binds," sharing its origin with the word religion. The ligand bumps onto the receptor and slips off, bumps back on, slips back off again. The ligand bumping on is what we call the binding, and in the process, the ligand transfers a message via its molecular properties to the receptor.
Ligand and receptor --- striking the same note and producing a vibration that rings a doorbell to open the doorway to the cell. What happens next is quite amazing. There receptor, having received a message, transmits it from the surface of the cell deep into the sell's interior, where the message can cane the state of the cell dramatically. A chain reaction of biochemical events is initiated and begin any number of activities --- manufacturing new proteins, making decisions about cell division, opening or closing ion channels, adding or subtracting energetic chemical groups like the phosphates --- to name just a few. In short, the life of the cell, what it is up to at any moment, is determined by which receptors are on its surface, and whether those receptors are occupied by ligands or not. These minute physiological phenomena at the cellular level can translate to large changes in behavior, physical activity, even mood.
The process of binding is very selective, very specific. In fact, we can say that binding occurs as a result of receptor specificity, meaning the receptor ignores all but the particular ligand that's made to fit it. The opiate receptor, for instance, can "receive" only those ligands that are members of the opiate group, like endorphins, morphine, or heroin. The Valium receptor can attach only to Valium and Valium-like peptides. It is this specificity of the receptors that allow for a complex systems of organization and insures that everything gets to where it's supposed to be going.
Ligands are generally much smaller molecules than the receptors, and they are divided into 3 chemical types:
Neurotransmitters, Steroid Hormone, Peptide Hormone
1. Neurotransmitters which are small molecules with such unwieldy names as acetylcholine, norepinephrine, dopamine, histamine, glycine, GABA, and serotonin. These are the smallest, simplest of molecules, generally made in the brain to carry information across the gap, or synapse, between one neuron and the next. Manystart out as simple amino acids, the building blocks of protein, and then get a few atoms added here and there. A few neurotransmitters are unmodified amino acids.
2. Steroids which include the sex hormones testosterone, progesterone, and estrogen. All steroids start out as cholesterol, which gets transformed by a series of biochemical steps into a specific kind of hormone. For example, enzymesin the gonads --- the testes / the ovaries --- change the cholesterol into the sex hormones, while other enzymes convert cholesterol into other kinds of steroid hormones, such as cortisol, which are secreted by the outer layer of the adrenal glands under stress.
3. Peptides constitute perhaps 95% of all ligands. Like receptors, peptides are made up of strings of amino acids, Visualize the following: if the cell is the engine that drives all life, then the receptors are buttons on the control panel, and a specific peptide (or other kind of ligand) is the finger that pushes that button and gets things started. These chemicals play a wide role in regulating practically all life processes, and are the other half of the equation of what I call the molecules of emotion.
But neuroscience was so focused for so long, on the concept of the nervous system as an electrical network based on neuron -axon-dendrite-neurotransmitter connections, that even when we had the evidence, it was hard to grasp the idea that the ligand - receptor system represented a second nervous system, one that operated on a much longer time scale, over much greater distances.
Especially difficult was that this chemical based system was one indisputable more ancient and far more basic to the organism.
There were peptides such as endorphins, for instance, being made inside cells long before there were dendrites, axons, over even neurons --- in fact, before there were brain.
Until the brain peptides were brought into focus by the discoveries of the 1970s, most of our attention had been directed toward neurotransmitters and the jump they made from one neuron to another, across the little moat known as the synaptic cleft.
The neurotransmitters seemed to carry very basic messages, either "on" or "off," referring to whether the receiving cell discharges electricity of not.
The peptides, on the other hand, while they sometimes act like neurotransmitters,swimming across the synaptic cleft, are much more likely to move through extra cellular space, swept along in the blood and cerebrospinal fluid, traveling long distances and causing complex and fundamental changes in the cells whose receptors they lock onto.
This then, was as much as we understood about the receptor and its ligand by 1972, before researchers had actually found a drug receptor and well before the breakthrough involving the immune system in 1984, which used receptor theory to define a bodyside network of information and to provide a biochemical basis for the emotions. In the wake of discoveries in the 1980s, these receptors and their ligands have come to be seen as "information molecules" --- the basic units of language used by cells though out the organism to communicate across systems such as the endocrine, neurological, gastrointestinal, and even the immune system.
Overall, the musical hum of the receptors as they bind to their many ligands, often in the far-flung parts of the organism, creates an integration of structure and function that allows the organism to run smoothly, intelligently.
A Brief History of Receptors
While the idea of the receptor mechanism had originated with pharmacologists in the early 20th century, many university physiology departments took it up as well because they found it a useful concept too explain the new chemical substances bing found in the nervous system --- the neurotransmitters. These chemical communicators, which were secreted across the synapse also functioned in a way that could be understood by the receptor-ligand model, even though biochemistry had yet to develop a way to measure wheat was happening.
The chemical formula of acetylcholine, the first neurotransmitter to be discovered, was still decades away from being diagrammed when physiologist Otto Loewi did early neurotransmitter experiments following a dream he had one night. These first experiments, performed in 1921, involved the action of a neurotransmitter on a frog heart.
Removed from the frog and placed still beating in a large beaker, the heart slowed down dramatically when Loewi applied juice extracted from the vagal nerve to it. The mysterious "vagusstuff" turned out to be the neurotransmitter acetylcholine. Made by the nerves, acetylcholine causes a slowing of the heartbeat and a rhythmic stimulation of the digestive muscles after heating, which together contribute to the feeling of relaxation.
For both of these processes, scientists theorized that there were acetylcholine "receptor sites," some on the heart muscles, others on the digestive tract muscles, and still others on voluntary skeletal muscles, but they couldn't actually demonstrate their existence.
Early 20th century theory became reality in 1972, Jean-Pierre Changeux addressed a pharmacology conference in England. With a dramatic flourish, the biochemist pulled from his breast pocket a tiny glass tube with a single narrow blue band across its middle. The tube contained pure acetylcholine receptors taken from the body of an electric eel and separated from all the other molecules and stained blue. This was the first time a receptor had been isolated in the lab.
A New Idea
My own work in "receptology" began in 1970, in the hall os the pharmacology department of Johns Hopkins University, where I was able to earn my doctoral degree studying gunner two of the world's experts on insulin receptors and brain biochemistry. At that time, the insulin receptor was the only receptor being studied with the new methods that had been developed for trapping the more slippery ligands, that is, those that did not stay irreversibly stuck to its receptors (like the snake toxin). There was a need to study other receptors to try to trap other kinds of ligands.
In my own filed, the prevailing dogma was that no drug could act unless fixed. It meant that if a drug worked, there had to be a receptor, and our job is to find it. The drugs we were studying at the time were drugs that obviously changed behavior --- I almost said consciousness, but bank then nobody used the C-word, except the hippies. Yet everyone recognized that these drugs, which included heroin, marijuana, Librium, and PCP (angel dust), precipitated a radical change in the emotional state, that is, altered the state of consciousness of those who used them. That's why, when I began my career in the early 1970s, such drugs were our main tool for studying the chemistry of the brain.
The problem was that our drugs were all from plants, and it was well known that once in the body these plant-derived ligands bound to receptors so briefly before exiting the body in the urine that they were difficult. The challenge I would eventually make my own was to use the new methodology to trap the small morphine molecule on its receptor in a test tube --- a receptor that many people didn't even believe existed. The proof that it did would have ramifications beyond my wildest dreams.
In completely unexpected ways, the discovery of the opiate receptor would extend into every field of medicine, uniting endocrinology, neurophysiology, and immunology, and fueling a synthesis of behavior, psychology, and biology. It was a discovery that touched off a revolution, a revolution that had been quietly under way for some time.
Dr. Candace Pert (1946-2013) was an internationally recognized neuroscientist and pharmacologist who published over 250 research articles and was a significant contributor to the emergence of Mind-Body Medicine as an area of legitimate scientific research in the 1980’s.
Dr. Pert appeared in the films What the Bleep Do We Know!?? and The People vs the State of Illusion and was an on air contributor to Bill Moyer’s TV program Healing and the Mind. She is the author of the books Molecules of Emotion, The Science Behind Mind-Body Medicine (Scribner, 1997) and Everything You Need to Know to Feel Go(o)d (Hay House, 2006). She also authored the musical guided imagery CD Psychosomatic Wellness: Healing your Body-Mind. and Healing the Hurting, Shining the Light, A Chakra Meditation for all your BodyMinds. Candace famously said “Your Body is your Subconscious Mind” and she believed the meditations and affirmations she wrote and produced in these CD’s would help you access subconscious patterns and reprogram them for better health.