PAGE 4 OF 6
The receptors were unknown until 1999, when research groups headed by Charles S. Zuker, an HHMI investigator at the University of California, San Diego, and Nicholas Ryba of the National Institutes of Health isolated the first candidate taste receptors, now known as T1R1 and T1R2. Then in 2000, Zuker, Ryba, and Buck reported the isolation of the receptors for bitter taste, collectively known as the T2Rs. More than 30 different T2Rs exist, reflecting the importance of avoiding a wide range of bitter substances, many of which are poisons. Notably, experiments by Zuker, Ryba, and colleagues demonstrated that the bitter taste receptors are a population of bitter-sensing cells in the tongue that trigger hardwired aversion signals.
If so, what explains the popularity of coffee, with its bitter caffeine taste, as well as beer and certain other bitter foods? For one thing, says Zuker, who likes darkly roasted coffee and takes it black, with sugar, "There is a reward associated with coffee and beer." For another, "We like to live on the edge and have new sensory experiences." Of course, individuals vary in their taste for bitter substances, causing some people to steer away from strong ales and to dose their coffee with cream and sugar.
Not long after the bitter-receptor discovery, Zuker and Ryba functionally characterized the receptors and cells for sweet and umami tastes; in the fall of 2006, the scientists reported that sour taste is detected by a completely separate population of taste cells expressing an ion channel protein called PKD2L1. The receptor for salt has still not been found.
Zuker concludes that taste coding in the tongue and mouth is configured with "elegant simplicity." He writes: "It is now clear that distinct cell types, expressing unique receptors, are tuned to detect each of the five basic tastes. And while certain areas of the tongue are more sensitive to some flavors than to others, every area can respond to every flavor."
A corollary that emerged from these studies is that taste is a property of the cells that are activated, not of the food molecules—or even the receptors. Zuker and colleagues inserted receptors for a tasteless opioid compound into the sweet-responsive cells of mice, and the animals reacted as if the compound tasted sweet. Zuker and Ryba also generated mice that taste bitter compounds as sweet. "There's nothing bitter about bitter tastants, and there's nothing sweet about sucralose (a sugar substitute)," observes Ryba. "It tastes sweet because when we put it on our tongue we get a particular pattern of neural firing."
Ultimately, Ryba and Zuker hope to trace taste signals from the tongue up into the brain, where they are mingled with olfactory and other sensory information, leading to cognitive and behavioral responses.
Communication via pheromones occurs in insects, fish, reptiles, and mammals—though whether they're significant in the lives of human beings is a fascinating and controversial question. "Pheromones have to do with making shortcuts in the brain to certain behaviors," explains HHMI investigator Catherine Dulac at Harvard University. "In a sense, these pheromones are a by-product of the animal's internal state," she says. "For example, if an animal has a high level of testosterone, the metabolites in its urine will be high and they act as a pheromonal signal of dominance" that goes out to both males and females in close proximity.
It has long been thought that pheromones may be sensed exclusively by the accessory olfactory system. In this system, chemicals are detected in the vomeronasal organ (VNO) in the nasal septum and signals are then transmitted through special pathways separate from those that carry odor signals. Most mammals and reptiles have a VNO, whereas if a VNO exists in humans at all, it is nonfunctioning.
While working in Axel's lab, Dulac in 1995 was the first to identify a family of receptors in the VNO. Two years later, the Buck and Ryba groups as well as Dulac at Harvard discovered a second family of VNO receptors. In further studies, Dulac identified additional components of the VNO signaling machinery.