Receptor is a molecule or portion of a molecule with which a hormone, neurotransmitter, or other biochemically active molecule interacts to initiate a response in a target cell.

Hormones are the chemical messengers of the endocrine system. Endocrine glands and tissues in various parts of the body produce these molecules, often at distances far from their ultimate site of action.

• Because of this, hormones must travel through the bloodstream to their targets, and the responses they produce can require anywhere from seconds to hours to begin.

Neurotransmitter is a chemical messenger that travels between a neuron and a neighbouring neuron or other target cell to transmit a nerve impulse.

Endocrine system is a system of specialized cells, tissues, and ductless glands that secretes hormones and shares with the nervous system the responsibility for maintaining constant internal body conditions and responding to changes in the environment.

Chemically, hormones are of three major types:

(1) amino acid derivatives, such as epinephrine

(2) polypeptides, which range from just a few amino acids to several hundred amino acids

(3) steroids, which are lipids with the distinctive molecular structure based on four connected rings common to all sterols.

Upon arrival at its target cell, a hormone must deliver its signal to create a chemical response inside the cell.

• The signal enters the cell in ways determined by the chemical nature of the hormone. Because the cell is surrounded by a membrane composed of hydrophobic molecules, only nonpolar, hydrophobic molecules can move across it on their own.

• The steroid hormones are nonpolar, so they can enter the cell directly by diffusion; this is one of the ways a hormone delivers its message. Once within the cell’s cytoplasm, a steroid hormone encounters a receptor molecule that carries it to its target, DNA in the nucleus of the cell.

• The result is some change in production of a protein governed by a particular gene.

The polypeptide and amine hormones are water-soluble molecules and cannot cross the hydrophobic cell membranes. Rather than entering cells, they deliver their messages by bonding noncovalently with receptors on cell surfaces.

• The result is release of a second messenger within the cell. There are several different second messengers, and the specific sequence of events varies.

• In general, three membrane-bound proteins participate in release of the second messenger: (1) the receptor and

  (2) a G protein (a member of the guanine nucleotide-binding protein family) that transfer the message to

  (3) an enzyme.

• First, interaction of the hormone with its receptor causes a change in the receptor. This stimulates the G protein to activate an enzyme that participates in release of the second messenger.

The main function of epinephrine in a “startle” reaction is a dramatic increase in the availability of glucose as a source of energy to deal with whatever stress is immediate. The time elapsed from initial stimulus to glucose release into the bloodstream is only a few seconds.

Epinephrine acts via cyclic adenosine monophosphate (cyclic AMP, or cAMP), an important second messenger. The sequence of events in this action illustrates one type of biochemical response to a change in an individual’s external or internal environment.

• Epinephrine, a hormone carried in the bloodstream, binds to a receptor on the surface of a cell.

• The hormone–receptor complex activates a nearby G protein embedded in the interior surface of the cell membrane.

• GDP (guanosine diphosphate) associated with the G protein is exchanged for GTP (guanosine triphosphate) from the cytosol.

• The G protein–GTP complex activates adenylate cyclase, an enzyme that also is embedded in the interior surface of the cell membrane.

• Adenylate cyclase catalyses production within the cell of the second messenger— cyclic AMP—from adenosine triphosphate (ATP).

• Cyclic AMP initiates reactions that activate glycogen phosphorylase, the enzyme responsible for release of glucose from storage. (Interaction of other hormones with their specific receptors results in initiation by cyclic AMP of other reactions.)

• When the emergency has passed, cyclic AMP is converted back to ATP.

Hormones that are amino acid derivatives are synthesized from amino acids. Epinephrine and norepinephrine act as hormones throughout the body and also act as neurotransmitters in the brain. Polypeptide hormones are the largest class of hormones.

Steroid hormones are classified as mineral corticoids, glucocorticoids, or sex hormones. All three types are synthesized from the endocrine system.

Neurotransmitters are synthesized in presynaptic neurons and stored there in vesicles for release when needed. They travel across a synaptic cleft to receptors on adjacent target cells. Some act directly via their receptors; others utilize cyclic AMP or other second messengers.

After their message is delivered, neurotransmitters are either broken down rapidly or taken back into the presynaptic neuron so that the receptor is free to receive further messages.

Acetylcholine is a neurotransmitter responsible for the control of skeletal muscles. It is also widely distributed in the brain, where it plays a role in the sleep–wake cycle, learning, memory, and mood. Cholinergic nerves rely on acetylcholine as their neurotransmitter.

• Acetylcholine is synthesized in presynaptic neurons and stored in their vesicles. The rapid sequence of events shows the action of acetylcholine communicating between nerve cells, and the sequence is as follows:

  • A nerve impulse arrives at the presynaptic neuron.

  • Vesicles move to the cell membrane, fuse with it, and release their acetylcholine molecules (several thousand molecules from each vesicle).

  • Acetylcholine crosses the synapse and binds to receptors on the postsynaptic neuron, causing a change in membrane permeability to ions.

  • This change in the permeability to ions of the postsynaptic neuron initiates the nerve impulse in that neuron.

  • After the message is delivered, acetylcholinesterase present in the synaptic cleft catalyzes the decomposition of acetylcholine.

  • Choline is absorbed back into the presynaptic neuron, where new acetylcholine is synthesized.

A drug is any molecule that alters normal functions when it enters the body from an external source. The action is at the molecular level, and it can be either therapeutic or poisonous. To have an effect, many drugs must connect with a receptor.

Pharmacologists classify some drugs as agonists—substances that act to produce or prolong the normal biochemical response of a receptor. Other drugs are classified as antagonists—substances that block or inhibit the normal response of a receptor.

Serotonin, norepinephrine, and dopamine are known as monoamines.

• The connection between major depression and a deficiency of serotonin, norepinephrine, and dopamine is well-established.

• The evidence comes from the different modes of action of three families of drugs used to treat depression: amitriptyline, phenelzine, and fluoxetine.

• Each in its own way increases the concentration of the neurotransmitters at synapses.

  • Amitriptyline is representative of the tricyclic antidepressants, which were the first generation of these drugs. The tricyclics prevent the re-uptake of serotonin and norepinephrine from within the synapse.

    • Serotonin is important in mood-control pathways and functions more slowly than other neurotransmitters; slowing its re-uptake often improves mood in depressed patients.

  • Phenelzine is a monoamine oxidase (MAO) inhibitor, one of a group of medications that inhibit the enzyme that breaks down monoamine neurotransmitters. This inhibition of MAO allows the concentrations of monoamines at synapses to increase.

  • Fluoxetine represents the newest class of antidepressants, the selective serotonin re-uptake inhibitors (SSRI). They are more selective than the tricyclics because they inhibit only the re-uptake of serotonin.

    • Fluoxetine (Prozac) has rapidly become the most widely prescribed drug for all but the most severe forms of depression. Most antidepressants cause unpleasant side effects; fluoxetine does not, a major benefit.

Dopamine plays a role in the brain in processes that control movement, emotional responses, and the experiences of pleasure and pain.

• It interacts with five different kinds of receptors in different parts of the brain.

• An oversupply of dopamine is associated with schizophrenia, and an undersupply results in the loss of fine motor control in Parkinson’s disease.