CHICAGO --- Striking new biochemical evidence that shows a link between alcoholism and nicotine addiction has been discovered by pharmacologists at Northwestern University Medical School.
Northwestern researchers reported that alcoholic beverages modify the activity of a neuronal nicotinic receptor -- the same target site in the nervous system that is altered by exposure to the nicotine in tobacco.
The study, published in the October 18 issue of the journal Neuroscience Letters, may help explain the high correlation between alcoholism and smoking. Although about 10 percent of the population are heavy smokers, other research shows that among alcoholics, 70 to 90 percent are heavy smokers.
One reason for this connection is that nicotine stimulates and then desensitizes the neuronal nicotinic acetylcholine receptor, according to Toshio Narahashi, who headed the study. Narahashi is the John Evans Professor of Pharmacology and the Alfred Newton Richards Professor at Northwestern University Medical School.
Narahashi and his colleagues showed that low concentrations of nicotine applied over a prolonged period desensitized the acetylcholine receptor without stimulating it.
"The acetylcholine receptor of the nicotine addict may be slightly desensitized, meaning that higher doses of alcohol are required to stimulate it," Narahashi said. More experiments must be done to prove this hypothesis, he said.
The researchers also found that alcohol affects the acetylcholine receptors at minute concentrations -- much lower than those reported for its other target sites in the nervous system.
"The potent action of alcohol on the neuronal nicotinic acetylcholine receptors suggests that alcohol and nicotine interact at this site. Our findings may also shed new light on the molecular mechanism of action of alcohol," Narahashi said.
Acetylcholine is a neurotransmitter, or chemical messenger, that affects a number of body systems, including the cardiovascular, gastrointestinal, urinary and respiratory systems. Receptors are usually protein molecules, either on or within a cell, that bind with neurotransmitters or hormones and cause a basic change in the structure of the molecule.
Other investigators have identified several sites for alcohol among various targets, i.e., neuroreceptors and ion channels, the tiny "pores" that promote or inhibit passage of sodium, calcium, potassium or chloride in and out of the cell membrane. However, alcohol's exact molecular mechanism of action on the nervous system remains controversial.
Narahashi noted that alcohol does act on a number of other target sites, but at high concentrations. This implies that the function of these channel systems is altered more in the later stages of alcohol intoxication, he said.
"The question thus arises as to what systems and mechanisms in the central nervous system are altered in the earlier stages of alcohol intoxication when the blood-alcohol concentrations are much lower, yet are sufficient to modify behavioral traits such as mood, attention and craving," he said.
Using cell models that contain ion channels and membrane receptors similar to those in humans and also release acetylcholine, Narahashi and his colleagues found that alcohol modified the kinetics of the neuronal nicotinic acetylcholine receptors at concentrations as low as 30 to 100 micromoles per liter, or at a potency 1,000 times higher than that for the other receptors and channels.
Their results suggest that neuronal nicotinic acetylcholine receptors may be important target sites of alcohol, particularly in the early stages of alcohol intoxication.
Another important point, Narahashi said, is that there are several subtypes of the neuronal nicotinic acetylcholine receptor that make up different combinations of receptor subunits. These subtypes are known to show various sensitivities to several drugs and play a number of physiological roles in the brain.
"It is likely that alcohol at low (micromolar) concentrations acts on a specific subtype or subtypes of acetylcholine receptor," he said.
Narahashi and his colleagues are now pursuing this line of research in the laboratory.
Narahashi's co-researchers on this study were Keiichi Nagata, Gary L. Aistrup, Chao-Sheng Huang, William Marszalec, and Jin-Ho Song, of the department of molecular pharmacology and biological chemistry, and Jay Z. Yeh, professor of molecular pharmacology and biological chemistry and of anesthesiology at Northwestern University Medical School.