Although a role for the gastric and intestinal mucosa in molecular sensing has been known for decades, the initial molecular recognition events that sense the chemical composition of the luminal contents has remained elusive. Here we identified putative taste receptor gene transcripts in the gastrointestinal tract. Our results, using reverse transcriptase-PCR, demonstrate the presence of transcripts corresponding to multiple members of the T2R family of bitter taste receptors in the antral and fundic gastric mucosa as well as in the lining of the duodenum. In addition, cDNA clones of T2R receptors were detected in a rat gastric endocrine cell cDNA library, suggesting that these receptors are expressed, at least partly, in enteroendocrine cells. Accordingly, expression of multiple T2R receptors also was found in STC-1 cells, an enteroendocrine cell line. The expression of ␣ subunits of G proteins implicated in intracellular taste signal transduction, namely G␣gust, and G␣t-2, also was demonstrated in the gastrointestinal mucosa as well as in STC-1 cells, as revealed by reverse transcriptase-PCR and DNA sequencing, immunohistochemistry, and Western blotting. Furthermore, addition of compounds widely used in bitter taste signaling (e.g., denatonium, phenylthiocarbamide, 6-n-propil-2-thiouracil, and cycloheximide) to STC-1 cells promoted a rapid increase in intracellular Ca 2؉ concentration. These results demonstrate the expression of bitter taste receptors of the T2R family in the mouse and rat gastrointestinal tract.stomach ͉ intestine ͉ gustducin ͉ transducin T he gustatory system has been selected during evolution to detect nutritive and beneficial compounds as well as harmful or toxic substances (1, 2). In particular, bitter taste has evolved as a central warning signal against the ingestion of potentially toxic substances (3). Recently, a large family of bitter taste receptors (T2Rs) expressed in specialized neuroepithelial taste receptor cells organized within taste buds in the tongue has been identified in humans and rodents (4-6). These putative taste receptors, which belong to the guanine nucleotide-binding regulatory protein (G protein)-coupled receptor superfamily characterized by seven putative transmembrane domains, are distantly related to V1R vomeronasal receptors and opsins (5). Genetic and biochemical evidence indicate that specific G␣ subunits, gustducin (G␣ gust ) and transducin (G␣ t ), mediate bitter and sweet gustatory signals in the taste buds of the lingual epithelium (7-11).Outside the tongue, expression of G␣ gust also has been localized to gastric (12) and pancreatic (13) cells, suggesting that a taste-sensing mechanism also may exist in the gastrointestinal (GI) tract. However, not all cells that express G␣ gust also coexpress members of the T2R family of receptors (5). For example, most G␣ gust -positive taste receptor cells in the lingual fungiform papillae are T2R-negative, implying that G␣ gust also could mediate signaling through other receptors (9). To establish that the gastric an...
We study the ON-OFF switching mechanism of oxide-based resistive–random–access–memories using theoretical calculations. Electron deficient vacancies (VO) up to 1+ charge states would stabilize a cohesive filament, while further electron removal will stabilize the disrupted VO configurations with 2+ charges. The VO cohesion-isolation transition upon carrier injection and removal is shown to be a strong driving force in the ON-OFF switching process. We also propose that bipolar or unipolar behavior is determined by how the carriers are injected into VO. The control of the carrier injection by the electrode material selection is essential for desired bipolar switching.
We present 350 m observations of 36 ultraluminous infrared galaxies ( ULIRGs) at intermediate redshifts (0:089 z 0:926) using the Submillimeter High Angular Resolution Camera II (SHARC-II) on the Caltech Submillimeter Observatory (CSO). In total, 28 sources are detected at S/ N ! 3, providing the first flux measurements longward of 100 m for a statistically significant sample of ULIRGs in the redshift range 0:1 P z P 1:0. Combining our 350 m flux measurements with the existing IRAS 60 and 100 m data, we fit a single-temperature model to the spectral energy distribution (SED) and thereby estimate dust temperatures and far-IR luminosities. Assuming an emissivity index of ¼ 1:5, we find a median dust temperature and far-IR luminosity of T d ¼ 42:8 AE 7:1 K and log (L FIR /L ) ¼ 12:2 AE 0:5, respectively. The far-IRYradio correlation observed in local star-forming galaxies is found to hold for ULIRGs in the redshift range 0:1 P z P 0:5, suggesting that the dust in these sources is predominantly heated by starbursts. We compare the far-IR luminosities and dust temperatures derived for dusty galaxy samples at low and high redshifts with our sample of ULIRGs at intermediate redshift. A general L FIR -T d relation is observed, albeit with significant scatter due to differing selection effects and variations in dust mass and grain properties. The relatively high dust temperatures observed for our sample compared to that of high-z submillimeter-selected starbursts with similar far-IR luminosities suggest that the dominant star formation in ULIRGs at moderate redshifts takes place on smaller spatial scales than is found at higher redshifts.
Somatostatin exerts multiple effects by activating distinct G protein-coupled receptors. Here we report the cellular sites of expression of the somatostatin subtype 2A (sst2A) receptor in the rat enteric nervous system by using a C-terminus-specific, affinity-purified antiserum and immunohistochemistry. Antibody specificity was confirmed by the cell surface staining of human embryonic kidney 293 cells expressing the sst2A receptor, the lack of staining of cells expressing the somatostatin subtype 2B receptor, and the abolition of staining by preincubating the antiserum with the C-terminus peptide used for immunization, SSt2A(361-369). The SSt2A receptor antibody recognized a broad 80 kDa band on Western blots of membranes prepared from cells transfected with sst2A receptor cDNA; following receptor membrane deglycosylation, the antibody detected an additional 40 kDa band. In the enteric nervous system, the sst2A antibody primarily stained neurons of the myenteric and submucosal plexuses, and abundant fibers distributed to the muscle, mucosa, and vasculature. Immunoreactive staining was also observed in non-neuronal cells, including presumed interstitial cells of Cajal of the intestine and enterochromaffin-like cells of the stomach. Fibers expressing sst2A receptor immunoreactivity were often in close proximity to D cells of the gastric and intestinal mucosa. Colocalization of somatostatin and sst2A receptor immunoreactivities was not observed in endocrine cells nor in enteric neurons. Double-label immunohistochemistry revealed colocalization of sst2A and vasoactive intestinal peptide immunoreactivities in enteric neurons. The multiple types of cells expressing the sst2A receptor, including enteric neurons and non-neuronal structures, in addition to the relationship between somatostatin and sst2A receptor elements, provide evidence that the sst2A receptor mediates somatostatin effects in the gastrointestinal tract via neuronal and paracrine pathways.
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