Molecular custodians sweep away odorants.

Molecular custodians sweep away odorants

The nose earns its keep by translating chemical stimuli into neural signals that ultimately convey, say, the smell of smoke or lasagna. Biochemically minded neuroscientists get paid for uncovering the molecular details of such feats.

In a seminar this week at the National Institutes of Health in Bethesda, Md., Israeli researcher Doren Lancet described studies at his lab and elsewhere revealing previously unrecognized biochemical players in the complex molecular dance underlying the sense of smell. Lancet, of the Weizmann Institute of Science in Rehovot, reports discovering several enzymes in the olfactory system's patch of receptive tissue--called the olfactory epithelium -- that closely resemble detoxification enzymes found in the liver and other body tissues. These olfactory-specific enzymes might be responsible for clearing molecular odor stimuli from the sensory tissue, Lancet says.

Most odorants are volatile, water-avoiding chemicals that readily penetrate oily cell membranes. As such, Lancet says, they should easily spread throughout the sensory epithelium, continuously stimulating the sensory cells. Yet electrode recordings from odorant-stimulated frog and rat olfactory tissue show that the cells stop responding within about a second after the odor source is removed.

Scientists have long imagined that this paradox might be solved by specific enzymes that transform odorants into nonodorants or remove them from the olfactory system. Lancet and his co-workers may have found some of those enzymes. "We identified several detoxification enzymes in the olfactory epithelium," he says. One is an olfactory-specific form of cytochrome P450, a group of Enzymes found in many body tissues that help detoxify chemicals that would otherwise remain inside cells to do biochemical mischief. The other is an olfactory-specific form of a different class of detoxification enzymes, known as the uridine diphosphate glucuronyl transferases, or UDPGTs. These typically pick up where a cytochrome P450 leaves off, transforming a water-avoiding molecule into a water-loving form readily cleared from tissue.

Lancet says he suspects that these enzymes, and similar ones still to be discovered in olfactory tissue, change excess odorant molecules into odorless, water-soluble forms that clear from the sensory epithelium. The researchers find the odor-eating enzymes in the glial cells that surround and support the sensory cells and in mucus-secreting cell assemblies called Bowman's glands, also located in the epithelium.

The resemblance of the olfactory forms of cytochrome P450 and UDPGT to known detoxification enzymes is not casual, Lancet suggests. In addition to helping clear out odorants, they may play a role in disarming potentially harmful chemicals, just as their enzymatic kin do in other tissues. Sensory epithelium is a penny-thin barrier between the nasal cavity and the brain, Lancet points out. "Wouldn't it be important," he asks, "for olfactory epithelium to carry a detoxification device such as these two enzymes in large amounts?"