Addiction Chemistry

Transmissions

Neurotransmitters are chemical messengers that transmit electrical signals across the gap between nerve cells. This gap or synapse, is an area of molecular real estate that drug researchers have been interested in for a long time.  Many drugs act at this location.

The efficiency and intensity of nerve transmissions are largely determined by the speed and duration of the signal, how fast the signal fades, and how quickly the cells return to their previous state.

The gap between adjoining nerve cells is an area devoid of physical contact. So inorder to convey messages the information must be exchanged in another way.

The transmission of information from one nerve to another is via the release of one of a series of neurotransmitters. These neurotransmitter are small chemicals that can quickly be synthesized or unassembled.

 

Transmitters are stored in tiny sacs or membrane bound vesicles. The arrival of electrical impulses called action potentials in the jargon of science, causes the vesicles to merge membranes with the nerve and empty its contents into the synaptic cleft. This activates the receptor on the forward side of the synapse. The action potential has thus jumped the gap and will start a new wave of depolorization via an action potential, which will need to be jumped and propagated until the instructions arrive at its final destination.

Nerve endings are specialized secretory machines that synthesize simple amino acid style transmitters (adrenaline, serotonin). Some code for slightly larger peptides that travel beyond the adjacent neuron to exert their effect.

 

Neurotransmitter have specific receptors that they can bind to. Serotonin, dopamine and endorphins are the main transmitters in the brain.

Neurotransmitters are synthesized, packaged and released by secretory vesicles. Once released they bind with their respective receptors throughout the brain. Their collective result determines a person’s drive, mood and perceptions.

Neurotransmissions also occur via small peptides called neuropeptides. These compounds, factors, secretagogue, or stimulating hormones, directly influence behavior.

 

Too little, too much or a defective neurotransmitter causes disorders like Parkinson's disease, depression and schizophrenia. These diseases are treated with pharmaceutical drugs that mimic the action of the deficient neurotransmitter, or they block the overabundant ones from activating their intended receptors.

 

Receptors for drugs are the same as the receptors for native molecules. They are studded along a cell’s membrane. They bind with drugs because of a drugs similarity to the natural or endogenously produced agent.

Serotonin for example can bind with at least 14 type of membrane receptors. Some receptors types are implicated in causing depression, obsessive-compulsive disorder and drug addiction. Others play a role in anxiety, aggression and sleep.

 

Receptors are capable of causing major changes by amplifying the signal via the genetic code due to access to the cell’s DNA. Their bindings are a series of on and off switched for genes.

 

Pharmacological management of disease involves inhibiting, blocking or in some other way restricting the binding of a receptor.  Its alternative method is to stimulate, amplify or prolong the binding of an opposing receptor.

G-Protein Receptors

The biological process by which all herbs, drugs and foods produce their effects is through the process of receptor binding. The effect of these substances is to emulate the natural transmitters that instill euphoria, improve mood, dull pain or in some other way cause the feeling of gratification.

Olfactory and gustatory stimuli for example, interact with their corresponding receptors to produce the senses of smell and taste.

 

Nature modulates the supply of neurotransmitters a type of receptor known as the G protein-coupled receptor (GPCR).

The GPCR is named for its ability to activate G proteins. The receptor actually splits G-protein into two active parts, an alpha subunit and a beta-gamma subunit.

 

The GPCR is a large family of proteins whose structure spans the entire width of a cell’s memebrane. Since the GPCR has access to both the internal and the external environment of the cell, transmembrane receptors can sense molecules outside the cell and activate the internal network to provide the appropriate response. Because of this dual activity, the G-protein-coupled receptors have become a prime target of drug research

 

The ligands that bind and activate the GPCR vary in size from small molecules to large proteins These ligand emanate from odors, taste, light, inflamamtion and immunity. These receptors can also bound to hormones, neurotransmitters and neuropeptides..

 

 

 

The G protein-coupled receptor is made up of seven membrane-spanning zones. These are the binding domains. These are the sites than can be activated by an external signal or ligand to cause a conformational change, or activation of the transmembraneous protein.

The G protein-coupled receptor is the design of choice for light and smell. These receptors provide the binding sites and consequently trigger the signals sent out by a library of chemical agents, growth factors and neuropeptides.

Include in this library are the compounds involved with hunger and appetite like leptin and neuropeptide Y. Other GPCRs include the regulators of reproduction like follicle-stimulating hormone and gonadotropic-releasing hormone. There are still others that effect metabolism like glucagon and thyrotropin-releasing hormone.

 

Inflammation is mediated via the activity of GPCRs and an assortment of prostanoids, chemotactic agents, leukotrienes and anaphylatic factors..

G-protein coupled receptors also bind with vasoactive compounds to regulate blood vesssel diameter, hence blood pressure, as well as vasopressin to regulate water balance.

G-protein coupled receptors in the brain bind with sensory signals as well as native opioids, and the neurotransmitters, dopamine and serotonin.

 

G-protein research has revealed a great deal about the way Nature simplified the process of regulatory control. The GPCR is the most elegant example of its systems of on and off switches. In the case of the G protein, the same molecule has multiple sites for binding. It the orchestration of these bindings that determines the end result.