By David N. Leff
If a bird should be so unwary as to devour a monarch butterfly (Danaus plexippus), it would promptly throw up. The larvae of those bright orange and black insects feed preferentially on plants of the milkweed family (Asclepiadaceae), from which they ingest extremely bitter cardiac glycosides. (As a drug, Digoxin, it¿s used to treat heart disease.)
The highly visible orange markings on the butterfly¿s wings and yellow-banded larvae are visible warnings to other predators to shun the carriers of this noxious chemical.
A vast variety of other plants practice similar chemical warfare against their wannabe foes by secreting toxic substances with sharp, acrid, repulsive bitter tastes. Caffeine and nicotine are familiar examples. Two synthetic bitter chemicals, sucrose octaacetate and denatonium benzoate, are used to denature grain alcohol.
Then there¿s propylthiouracil (¿prop¿ for short), which has two disparate uses. One is as a powerful ¿ and bitter ¿ drug for treating thyroid disease. Among its adverse side effects are nausea and loss of taste. Prop is also the traditional standby of population geneticists who study the genetics of taste perception in humans.
¿It¿s been known for a long time now from behavioral work,¿ observed neurobiologist Stuart Firestein at Columbia University, New York, ¿that populations differ in sensitivity to this particular bitter substance called prop. If you ask large numbers of people to taste little pieces of paper that have prop on them, some individuals don¿t taste it at all. And some others will retch from the taste of prop, it¿s so awful, so bitter.¿
This familiar phenomenon suggested to taste scientists, Firestein pointed out, ¿that the variable response was due to a single gene locus, because of the way it¿s distributed in the population. And this in turn hinted that there was a gene somewhere on the human genome that had something to do with bitter sensitivity.¿
That hint led Harvard Medical School neurobiologist Linda Buck to a discovery reported in today¿s issue of Nature, dated April 6, 2000. Its title tells her story: ¿A family of candidate taste receptors in human and mouse.¿ Firestein authored the ¿News & Views¿ commentary on her paper, titled ¿The good taste of genomics.¿
Buck told BioWorld Today: ¿The novelty of this work is identification of receptors for taste. Using those receptors, we can now begin to understand how different, diverse, bitter chemicals are detected in the tongue. We can also now use the genes encoding these receptors as molecular tools, to start exploring how information about different chemicals that we can taste is organized in the mouth and in the brain, to finally yield perception.¿
Taste Buds Only Tiny Fraction Of Tongue Surface
¿That novel discovery of taste receptors,¿ Firestein told BioWorld Today, ¿has been very difficult to achieve, largely because only a very small part ¿ less than 1 percent ¿ of the surface area of the tongue is involved in taste. So there¿s been a lack of tissue to work with, and it was hard to track down those receptors by your standard molecular mechanisms.¿ (See BioWorld Today, Aug. 24, 1999, p. 1.)
To get around this hang-up, he added, ¿It so happens, fortunately, that there is now in the human genome sequence database a significant amount of sequence in the chromosomal area around where we knew the prop gene was located.¿
Buck and her co-authors based their receptor discovery on this four-point game plan:
¿ Taste receptors would be encoded by a family of related genes;
¿ Some of those genes would be found at genetic loci associated with the ability of humans and mice to taste specific compounds;
¿ Taste receptors would be G protein-coupled receptors;
¿ Taste receptor genes might be found by using the Human Genome Project.
Buck foresees that ¿the possible application would be to block these receptors, thus eradicating the bitter taste of medicines, and hopefully leading to better compliance in the administration of oral drugs to patients.¿ She and her group do not plan to pursue the development of such inhibitors, but she observed, ¿I imagine there will be people ¿ perhaps in the pharmaceutical industry ¿ who will be interested in doing that, on the basis of this new discovery of ours.¿
Firestein pointed out that many medicines could benefit by such a bitterness-receptor inhibitor. ¿For example, a large number of the more effective AIDS drugs are quite bitter tasting, even in capsule form. And in children it¿s still an issue because they just won¿t swallow pills. They need to have a liquid, yet cough syrup and aspirin derivatives ¿ such as ibuprofen ¿ are very bitter, so they get flavored up with these horrible taste additives.
¿There are a large number of pharmaceuticals,¿ he observed, ¿that you would get quicker and more efficient relief from if you could let them dissolve in your mouth. But you can¿t because of the bitter taste. Aspirin is a good example. For most of us it¿s extremely bitter. And one of the reasons it takes about 15 minutes or so for an aspirin tablet to get rid of a headache is because of the tortuous path it takes through your digestive system. If you could simply put an aspirin under your tongue, you¿d have an almost immediate effect ¿ relief within a minute.¿
Insects Have Taste Receptors On Wings, Legs, Feet
As for agricultural crop applications, Firestein noted that a Yale molecular entomologist has recently ¿discovered taste receptors in insects ¿ particularly in Drosophila, the fruit fly. Like Buck¿s group, he also employed a somewhat similar mechanism by scanning the database. He pulled out another family of taste receptors from the fly, and these could be extremely important because many insects choose their feeding or breeding hosts by virtue of taste.
¿Many insects have taste organs on their legs and wings,¿ Firestein added, ¿not just on their mouth parts. So they will actually sit on a plant and detect it right through their legs or feet or wings.
¿Used as either repellants or attractants, taste-receptor blockers could be very useful in controlling insect pests. The problem with insects is you don¿t want to use high concentrations of toxic insecticides on a crop, but if you could attract the insects into a trap using a taste attractant, then you could use very high concentrations of toxic substances, and it wouldn¿t be a problem.¿