As it is known, smokers become addicted because of nicotine. Nicotine addiction has historically been one of the hardest addictions to break. Wider studies have finally culminated in an explanation for nicotine's great affinity for brain receptors and the addictive molecule's almost total slight for the nicotine receptors found in muscle tissues.
Researchers said that: "Nicotine addiction begins with high-affinity binding of nicotine to acetylcholine receptors in the brain. The end result is over 4,000,000 smoking-related deaths annually worldwide and the largest source of preventable mortality in developed countries. Stress reduction, pleasure, improved cognition and other central nervous system effects are strongly associated with smoking."
The researchers point out that if nicotine were to activate its receptors in muscle tissue as potently as it does in the brain, cigarettes smoking would trigger intolerable and potentially lethal muscle contractions. This discrimination between the effects of nicotine on brain and muscle has puzzled biomedical researchers for years.
Scientists hold now a new research for to underlying chemical nature of addiction to tobacco and also for to offer an explanation as to why a single cigarette, despite nicotine's predicted toxicity does not kill a smoker immediately.
Chemist Dennis Dougherty and biologist Henry Lester of the California Institute of Technology, in Pasadena, California, have studied nicotine and its physiological effects. They also investigated how membrane-bound proteins interact with nicotine, and other small molecules.
Now, Dougherty and his team believe the explanation lies in how a specific interaction between nicotine and its receptor takes place.
Their structural studies, which combine organic synthesis, molecular biology, electrophysiology, and computer modeling, can reveal how changes in amino acids might affect the affinity of a given protein for a particular substrate.
They have used their expertise in this area to switch amino acids in the receptor and to show that the positive charge on the nicotine molecule has an affinity for a specific aromatic amino acid, tryptophan, in the box region of the receptor found in the brain. Although the receptor found in muscle tissue is broadly similar this so-called "cation-pi" interaction does not occur in muscle because there is a delicate difference between the binding pockets in each receptor, the lysine is missing and a glycine takes its place in the receptor box region.
Dougherty told: "TrpB makes a cation-pi interaction to the positive charge of nicotine in the brain receptor; but this strong binding interaction is absent in the muscle receptor. The lysine of interest is a bit remote to the binding site, but it influences the shape of the binding site so the nicotine can cosy up to TrpB."
Neuroreceptors, of which the nicotine receptor is just one example, are integral membrane proteins involved in memory, learning, and sensory perception.
Learning how they behave will not only clarify the people’s understanding of biology but could provide new targets for pharmaceuticals intended to treat Alzheimer's disease, Parkinson's disease, schizophrenia, learning and attention deficits, and many others disorders.
The team used genetic manipulation and measured neuronal activity in mice, which revealed how nicotine stimulates the brain's sensory systems via different pathways.
This is the first study to explore both the peripheral taste pathways activated by nicotine, and how these pathways are integrated in sensory areas of the human brain.