Nicotine works inside cells to boost addiction

When a person takes a puff from a cigarette, nicotine floods the brain, locks into receptors on the surface of the neurons, and produces feelings of happiness. But nicotine does not just stay on the surface of the cells, it penetrates the nerve cells and changes them from the inside to the outside.

A team of scientists has developed a protein sensor that lights up in the presence of nicotine, allowing researchers to observe nicotine movements in cells and reveal more about the nature of nicotine addiction! The study was conducted by Henry Lester, a biology professor at Caltech, and the study describing the study appears in General Physiology.

The endoplasmic reticulum is the part where proteins are synthesized and packaged to be transported to various other sites both inside and outside the cell. Nicotinic receptors (nAChRs) are among these proteins that are made in the endoplasmic grid and migrated to the surface of the cell.

When nicotine molecules enter the body, they travel through the bloodstream and reach the brain cells where they encounter nicotinic receptors (nAChRs) on the surface of these cells. This activates cell processes to release chemicals of reward and happiness.

However, what happens when nicotine has been moved to cells was not fully understood. Lester and his team previously found that some nicotinic receptors (nAChRs) remain in the endoplasmic reticulum - where they can also bind to nicotine.

Hoping to gain knowledge about the effects of nicotine in cells, Leicester and his team have developed a tool called a biosensor to illustrate where nicotine is collected in cells.

The biosensor consists of a specific protein and an inactivated fluorescent protein that can be opened and closed. While it is designed to close around nicotine and then activate the fluorescent protein to shine in intense ways, indicating where the nicotine molecules are and how many are present.

Scientists placed the biosensors on specific parts of the cell, specifically the endoplasmic reticulum and cell surfaces, and watched them illuminate as they flooded with nicotine.

The team discovered that nicotine enters the endoplasmic reticulum within a few seconds of its occurrence outside the cell. In addition, nicotine levels are well enough to affect nicotinic receptors (nAChRs) during their assembly and travel to the cell surface.

As a result, neurons become more sensitive to nicotine, which enhances the feelings of reward after a puff of a cigarette or an electronic cigarette. In other words, the more one smokes, the more quickly and easily the smoker gets the nicotine. This is part of the nicotine addiction.

References:

http://jgp.rupress.org/content/151/6/738/tab-article-info    DOI https://doi.org/10.1085/jgp.201812201