Neuroscience Basics (page 1) (page 2)
4. Neurotransmitter receptors
Neurotransmitters migrate across a synapse and interact with the appropriate neurotransmitter receptor. Receptors are relatively large proteins composed of different shapes that fit a unique neurotransmitter, much like a lock and key. This "lock and key" selectivity, based on neurotransmitter binding profiles, was used to identify and characterize the currently known neurotransmitter receptors. For example, serotonin will only bind to serotonin receptors, not dopamine receptors. Here is where it becomes extremely complicated. Serotonin, for example, can interact with more than 15 different serotonin receptors classified in distinct families. Some serotonin receptors function to excite neurons whereas others could be considered inhibitory. Now, how would a neuron with a single family of serotonin receptors function differently than a neuron with two different serotonin receptors? How would a neuron with both serotonin and GABA receptors function? As you may imagine, different combinations of neurotransmitter receptors adds a tremendous amount of neuronal diversity. Receptors, as broadly defined, can have very different functions including ion-channels, G protein-coupled receptors, and transporters.
The primary function of ion channels is to regulate electrical properties of neurons with a very rapid response time. Ligand-gated ion channels regulate ion passage through interactions with neurotransmitters. Examples include NMDA receptors that bind glutamate to regulate sodium, potassium, and calcium ions and GABA receptors that bind GABA to regulate chloride ions. The drugs of abuse ketamine and PCP block NMDA receptor function whereas benzodiazepines, often used to treat anxiety, are a class of drugs that enhance the activity of GABA receptors. In contrast to ligand-gated channels that are regulated by neurotransmitters, voltage-gated ion channels open and closes in response to changes in membrane potential (voltage inside relative to outside of a cell) and are named for the ion (e.g. potassium) that passes through its pore. A third type of ion channel, termed resting channel, is responsible for establishing the polarized state of a cell, known as the resting potential. The typical resting potential of a neuron ranges from -60 to -70 mV (more negative inside a cell). Thus, depolarization refers to membrane potentials that are more positive than the resting potential whereas hyperpolarization signifies more negative.
G protein-coupled receptors can modify the electrical properties of a neuron, but the response time is much slower than ion channels. A primary function of G protein coupled receptors is the regulation of intracellular signaling pathways involving diverse second messengers such as cyclic nucleotides and metabolites of membrane lipids. A "G protein" is an accessory molecule that directly activates (or inhibits) second messenger pathways. There are many different G proteins. Families of receptors are classified based on which second messenger pathway is primarily regulated. Although each receptor strongly activates a single pathway, most receptors have the potential to interact with more than one class of G protein, resulting in weak activation of additional pathways. Many of the G protein coupled receptors, including serotonin and dopamine, are targets of the atypical antipsychotic drugs that are used to treat schizophrenia.
The primary job of proteins called neurotransmitter transporters is to gather the released neurotransmitter and bring it back into the pre-synaptic neuron. The lifetime of a neurotransmitter, once released into the synapse, is very short. As with the receptors, the transporters interact with a specific neurotransmitter (serotonin, norepinephrine, dopamine, or GABA). Neurotransmitter transporters, particularly serotonin and norepinephrine, are targets of the "SSRI" class of antidepressants that block transporter function. Drugs that block a transporter cause delayed clearance of a neurotransmitter from the synapse.
5. Pharmacology: agonist or antagonist
Pharmacologists use the descriptive terms agonist or antagonist to classify drugs that activate (turn on) or inhibit (turn off), respectively, the function of a particular receptor. Additional terms are used to more precisely define the activity of drugs, but they are not important for this discussion. In contrast to neurotransmitters, synthetic drugs could be an antagonist (or agonist) at several different receptors, which is a common property of atypical antipsychotic drugs.
6. "Natural"
Natural is broadly defined as occurring in nature. However, the context of natural must be carefully considered. A compound derived from a plant is considered natural to a plant, but probably not to humans. A more useful term would be "endogenous". For example, serotonin is an endogenous compound in humans because humans make it. A natural (or endogenous) compound taken as a medication has the potential to be harmful to humans. Please discuss safety issues carefully with a health care provider before taking any medications, whether natural or synthetic.
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