Ion channels and second messengers involved in transduction
and modulation of sweet taste in mouse taste cells*
Kumiko Sugimoto1,**, Noriatsu Shigemura2, Keiko
Yasumatsu2, Rie Ohta2, Kiyohito Nakashima3,
Kirio Kawai4, and Yuzo Ninomiya2
1Section of Molecular Neurobiology, Graduate School,
Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo
113-8549, Japan; 2Section of Oral Neuroscience, Graduate School of Dental
Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582,
Japan; 3Department of Chemistry, Asahi University School of Dentistry,
1851-1 Hozumi, Motosu-gun, Gifu 501-0296, Japan; 4Department of Anatomy
(Division II), School of Dental Medicine, Tsurumi University, 2-1-3
Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan
Abstract: Leptin, a hormone released from the adipose
tissue, inhibits food intake and increases energy expenditure. We have
found a novel function of leptin as a modulator of sweet taste sensitivity
in mice. In lean normal mice, the gustatory nerve responses to sweet
stimuli were selectively suppressed depending on plasma leptin level
after an intraperitoneal injection of recombinant leptin. Patch-clamp
studies using isolated taste cells of lean mice showed that extracellular
leptin enhanced K+ currents of sweet-responsive taste cells,
which led to membrane hyperpolarization and a reduction of sweetener-induced
depolarization. Reverse transcription-polymerase chain reaction (RT-PCR)
and in situ hybridization analyses demonstrated specific expression
of mRNA of the long-form functional leptin receptor (Ob-Rb) in taste
tissue and cells of lean mice. The genetically diabetic db/db
mice, which have defects in Ob-Rb, demonstrated neither a suppression
of gustatory neural responses to sweeteners nor an increment of whole-cell
K+ conductance of taste cells even with high doses of leptin.
These results suggest that Ob-Rb is specifically expressed in sweet-responsive
taste cells of lean mice and that leptin suppresses sweetener-induced
depolarization via activation of K+ channels, leading to
a decrease in impulses of sweet-best fibers. The enhanced sweet responses
of db/db mice may result from the lack of inhibitory modulation
by leptin.
* A special topic issue on the science
of sweeteners.
** Corresponding author.