Bitter Pill

Editor's choice in drug discovery

By | March 1, 2011

3D4MEDICAL / PHOTO RESEARCHERS INC.The paper

D.A. Deshpande et al., “Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction,” Nat Med, 16:1299-304, 2010. Free F1000 Evaluation

The finding

Stephen Liggett and colleagues at the University of Maryland School of Medicine set out to identify the G-protein coupled receptors (GPCRs) involved in the contraction of bronchial airway muscles that can lead to asthma. They discovered bitter taste receptors—previously only found on the tongue—on airway smooth muscle (ASM) cells, and showed that their activation causes bronchial relaxation instead.

The surprise

Liggett thought these receptors might protect against inhaled toxic substances. When his lab treated ASM cells with bitter-tasting compounds, such as saccharin or chloroquine, they saw an increase in intracellular calcium concentration—a hallmark of smooth muscle contraction, and thus presumably of bronchoconstriction. “We were thinking we’d found the cause of occupational asthma,” Liggett says. Surprisingly, when they tested the bitter substances on surgical tissue explants, they saw the muscles relax.

The relaxation

The bitter-tasting molecules very rapidly activated highly localized stores of calcium, rather than the slower, cell-wide calcium release that causes constriction. The team repeated the test in live mice, and saw the same result. “It was like nothing we had ever seen before,” Liggett says.

The drugs

There are “10,000 or more” known activators of bitter taste receptors, some of which are already used in medicine. The only issue would be making them more palatable, but that doesn’t bother Liggett much. “We’ve got more compounds than we can study,” he says.

F1000 evaluators: J. Martin (McGill Univ) E. Schneider & P. Murphy (NIAID) B. Nilius (KU Leuven)A. Morris & D. Spina (King’s Col London)

Add a Comment

Avatar of: You

You

Processing...
Processing...

Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo

Popular Now

  1. How Gaining and Losing Weight Affects the Body
    Daily News How Gaining and Losing Weight Affects the Body

    Millions of measurements from 23 people who consumed extra calories every day for a month reveal changes in proteins, metabolites, and gut microbiota that accompany shifts in body mass.

  2. That Other CRISPR Patent Dispute
    Daily News That Other CRISPR Patent Dispute

    The Broad Institute and Rockefeller University disagree over which scientists should be named as inventors on certain patents involving the gene-editing technology.

  3. EPO Revokes Broad’s CRISPR Patent
    The Nutshell EPO Revokes Broad’s CRISPR Patent

    Shortly after ruling out the earliest priority dates on a foundational patent for CRISPR gene-editing technology, the European Patent Office rescinded the patent entirely—and more are likely to follow.

  4. Learning Opens the Genome
    Daily News Learning Opens the Genome

    Researchers map learning-induced chromatin alterations in mouse brain cells, and find that many affect autism-associated genes.

AAAS