Nicotine's effects are receptor specific

Following chronic nicotine exposure, nicotine receptors increase in number, an upregulation that contributes to nicotine's addictive properties.

While a current belief is that this process is independent of the type of nicotine receptor, researchers have now uncovered this is not the case: the transient and prolonged changes in the nicotine levels of smokers each affect a specific receptor subtype.

The predominant subtype of nicotine receptor in the brain is known as A4B2; these receptors upregulate as nicotine levels gradually rise in the blood. Generally, they start increasing about 2-3 hours following exposure and peak after about 20 hours.

Due to lower prevalance, the upregulation –if any—of minor nicotine receptor subtypes has been difficult, but William Green and colleagues successfully developed cells expressing A6B2 nicotine receptors. They then demonstrated this class also undergoes nicotine upregulation, but at a much faster rate; A6B2 receptors increase within minutes of exposure and peak after only 2 hours.

These receptors also required about 10 times as much nicotine to stimulate as A4B2 receptors, a level that would only be reached during the brief spikes in nicotine levels occurring during smoking. These results offer new insights into the different phases of smoking, highlighting that separate receptors modulate the immediate and long term effects of nicotine.