The neuropeptide cholecystokinin (CCK) is thought to be involved in mediating the sensation of bitter taste. Now, a research team led by Herness has shown that neuropeptide Y (NPY) is also expressed by most of the CCK-expressing cells in taste buds and has the opposite physiological effects to those of CCK. These findings might shed new light on the intricate orchestration of chemical signals that are important for the tongue's ability to differentiate bitter and sweet tastes.

Taste buds are clusters of 50–100 differentiated epithelial cells. Sensory afferent nerve fibres connect each bud to the brain to transmit signals about taste. Only a minority of cells in each bud form synaptic contacts with these fibres, and how other cells send signals to the brain has been the focus of intense academic curiosity.

The researchers believe that neuropeptides might be part of the answer. Having established the role of CCK in taste transduction, they moved on to study other neuropeptides and found that NPY was also expressed in a subset of taste bud cells at both the mRNA and protein levels. This prompted them to test the physiological effects of NPY on taste bud cells isolated from rat tongues.

In contrast to CCK, NPY enhances inwardly rectifying potassium currents (Kir) in some taste bud cells and has no effect on intracellular calcium concentrations. The NPY-mediated Kir enhancement can be mimicked by NPY1 receptor agonists and is blocked when the cells are treated with NPY1 receptor antagonists, indicating that the effect of NPY might be mediated by the NPY1 receptor subtype.

If CCK and NPY have contrasting physiological effects, one simple hypothesis could be that they are expressed by non-overlapping subsets of taste bud cells and are responsible for transducing bitter and sweet tastes, respectively. However, the researchers found that 68% of cells that expressed CCK also expressed NPY, and 95% of cells that expressed NPY expressed CCK. In other words, a subset of taste bud cells releases both neuropeptides.

Therefore, the brain might sense bitter and sweet tastes as a result of two competing signalling pathways: CCK and NPY might excite the transduction of one taste and, at the same time, suppress that of another. Alternatively, the same subset of taste bud cells might release only one neuropeptide in response to either bitter or sweet tastes, despite being able to release both.