Organic Cation Transporter 3 (OCT3), also known as Solute Carrier Family 22 Member 3 (SLC22A3), is a protein that moves substances across cell membranes. It functions as a delivery system for various molecules, helping to control what enters and exits cells.
Understanding OCT3
OCT3 is a protein found embedded within cell membranes. Its primary function involves facilitating the movement of specific molecules called “organic cations” across these cellular barriers. It has 12 predicted membrane-spanning domains, allowing it to cross the cell membrane multiple times.
An organic cation is an organic molecule, meaning it contains carbon, that carries a positive electrical charge. These molecules cannot easily pass through the fatty layer of the cell membrane on their own. OCT3 enables these charged organic molecules to move into or out of cells. This movement is a form of facilitated diffusion, meaning it moves substances down their concentration gradient without directly using cellular energy.
Where OCT3 Operates
OCT3 is widely distributed throughout the body, found in numerous tissues and organs. High levels of OCT3 messenger RNA (mRNA) are observed in the kidney, liver, placenta, heart, and skeletal muscle.
In the brain, OCT3 is expressed in neurons, glial cells, epithelial cells of the choroid plexus, and areas like the hippocampus, hypothalamus, and amygdala, where it is involved in regulating neurotransmitter levels. In the liver and kidneys, OCT3 participates in eliminating drugs and toxins from the body. Within the placenta, OCT3 helps maintain serotonin balance between mother and fetus, protecting against serotonin-induced blood vessel constriction.
Molecules OCT3 Moves
OCT3 transports a variety of molecules, categorized as either endogenous (originating within the body) or exogenous (from outside the body). Among endogenous compounds, OCT3 transports monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin. It also transports histamine, certain hormones, and steroids.
Exogenous compounds transported by OCT3 include a wide array of drugs and environmental toxins. For instance, OCT3 transports common medications like the anti-diabetic drug metformin and anti-cancer drugs such as doxorubicin. It also handles recreational and pharmaceutical drugs like MDMA, amphetamine, methamphetamine, and cocaine.
OCT3’s Impact on Health
OCT3 influences health through its involvement in drug disposition, drug-drug interactions, and various health conditions. Its role in drug disposition means it affects how drugs are absorbed, distributed, and eliminated. For example, OCT3 on the basolateral membrane of hepatocytes in the liver and proximal tubular cells in the kidney helps with compound uptake.
OCT3 also contributes to drug-drug interactions, where one medication can alter the transport and effectiveness of another. Certain drugs can inhibit OCT3’s activity, potentially leading to altered levels of co-administered medications that rely on OCT3 for transport. This can influence drug efficacy and the potential for adverse effects.
Alterations in OCT3 function or expression have been linked to several health conditions. In neurological disorders, OCT3 helps regulate neurotransmitter levels in the brain, and its dysfunction can contribute to conditions like depression and anxiety. In the heart, OCT3 is involved in the uptake of norepinephrine, necessary for cardiac contractility. Decreased OCT3 expression in the liver, often due to conditions like cholestasis or liver fibrosis, can reduce the uptake of drugs like metformin, affecting their therapeutic action. Research suggests that OCT3 could be a target for developing new therapies for conditions such as diabetes and certain cancers.