Adenosine enhances sweet taste through A2B receptors in the taste bud

• Published in: The Journal of neuroscience 2012-01, Vol.32 (1), p.322-330
• Main Authors: Dando, Robin, Dvoryanchikov, Gennady, Pereira, Elizabeth, Chaudhari, Nirupa, Roper, Stephen D
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; Adenosine - physiology; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - secretion; Animals; CHO Cells; Cricetinae; Cricetulus; Female; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Organ Culture Techniques - methods; Receptor, Adenosine A2B - drug effects; Receptor, Adenosine A2B - genetics; Receptor, Adenosine A2B - physiology; Sweetening Agents - pharmacology; Taste - drug effects; Taste - physiology; Taste Buds - drug effects; Taste Buds - metabolism; Taste Buds - secretion
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.4070-11.2012

Mammalian taste buds use ATP as a neurotransmitter. Taste Receptor (type II) cells secrete ATP via gap junction hemichannels into the narrow extracellular spaces within a taste bud. This ATP excites primary sensory afferent fibers and also stimulates neighboring taste bud cells. Here we show that extracellular ATP is enzymatically degraded to adenosine within mouse vallate taste buds and that this nucleoside acts as an autocrine neuromodulator to selectively enhance sweet taste. In Receptor cells in a lingual slice preparation, Ca(2+) mobilization evoked by focally applied artificial sweeteners was significantly enhanced by adenosine (50 μM). Adenosine had no effect on bitter or umami taste responses, and the nucleoside did not affect Presynaptic (type III) taste cells. We also used biosensor cells to measure transmitter release from isolated taste buds. Adenosine (5 μM) enhanced ATP release evoked by sweet but not bitter taste stimuli. Using single-cell reverse transcriptase (RT)-PCR on isolated vallate taste cells, we show that many Receptor cells express the adenosine receptor, Adora2b, while Presynaptic (type III) and Glial-like (type I) cells seldom do. Furthermore, Adora2b receptors are significantly associated with expression of the sweet taste receptor subunit, Tas1r2. Adenosine is generated during taste stimulation mainly by the action of the ecto-5'-nucleotidase, NT5E, and to a lesser extent, prostatic acid phosphatase. Both these ecto-nucleotidases are expressed by Presynaptic cells, as shown by single-cell RT-PCR, enzyme histochemistry, and immunofluorescence. Our findings suggest that ATP released during taste reception is degraded to adenosine to exert positive modulation particularly on sweet taste.