B. Mosinger

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Papers by B. Mosinger

S11.2 Role of gustducin, taste receptors and transient receptor potential channel M5 in gastrointestinal chemosensation

Autonomic Neuroscience, 2009

coupled receptors and associated the G proteins shown to mediate taste modalities in the lingual ... more coupled receptors and associated the G proteins shown to mediate taste modalities in the lingual epithelium. Gut endocrine cells may also be able to detect the presence of microbes, via expression of bacterial recognition receptors such as toll-like receptors, or receptors for bacterial products, such as short chain fatty acids. Given the diversity of molecules that are detected at the luminal surface of gut endocrine cells and the effects on food intake and plasma glucose, make these cells attractive targets for the development of specific molecules that may be useful for body weight regulation and improved glucose homeostasis.

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Gustducin couples fatty acid receptors to GLP-1 release in colon

American Journal of Physiology-Endocrinology and Metabolism, 2013

Sweet taste receptor subunits and α-gustducin found in enteroendocrine cells of the small intesti... more Sweet taste receptor subunits and α-gustducin found in enteroendocrine cells of the small intestine have been implicated in release of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in response to glucose and noncaloric sweeteners. α-Gustducin has also been found in colon, although its function there is unclear. We examined expression of α-gustducin, GLP-1, and GIP throughout the intestine. The number of α-gustducin-expressing cells and those coexpressing α-gustducin together with GLP-1 and/or GIP increased from small intestine to colon. α-Gustducin also was coexpressed with fatty acid G protein-coupled receptor (GPR) 40, GPR41, GPR43, GPR119, GPR120, and bile acid G protein-coupled receptor TGR5 in enteroendocrine cells of the colon. In colon, GPR43 was coexpressed with GPR119 and GPR120, but not with TGR5. Treatment of colonic mucosa isolated from wild-type mice with acetate, butyrate, oleic acid, oleoylethanolamide, or...

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Phenoxy Herbicides and Fibrates Potently Inhibit the Human Chemosensory Receptor Subunit T1R3

Journal of Medicinal Chemistry, 2009

We show that phenoxy-auxin herbicides and lipid-lowering fibrates inhibit human but not rodent T1... more We show that phenoxy-auxin herbicides and lipid-lowering fibrates inhibit human but not rodent T1R3. T1R3 as a co-receptor in taste cells responds to sweet compounds and amino-acids; in endocrine cells of gut and pancreas T1R3 contributes to glucose sensing. Thus, certain effects of fibrates in treating hyperlipidemia and type II diabetes may be via actions on T1R3. Likewise, phenoxy-herbicides may have adverse metabolic effects in humans that would have gone undetected in studies on rodents.

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Roles of gustducin, taste receptors and transient receptor potential channel M5 in gut

Chemical Senses

Effect of insulin, thyroxine and oestradiol on growth of normal human diploid cells and human heteroploid HeLa cells

Physiologia Bohemoslovaca, 1983

Insulin (5 micrograms/ml), thyroxine (1 microgram/ml) and beta-oestradiol (0.1 microgram/ml), if ... more Insulin (5 micrograms/ml), thyroxine (1 microgram/ml) and beta-oestradiol (0.1 microgram/ml), if added separately to the medium, did not significantly influence the growth of normal human diploid LEP 19 cells cultivated in Eagle's MEM medium with 1% foetal calf serum. Combined, they did not influence the growth of LEP 19 cells in serum-free MEM medium either. Under the same cultivation conditions, insulin caused 37%, thyroxine 24% and a mixture of insulin, thyroxine and beta-oestradiol 325% (without serum) or 15% (with 1% foetal calf serum) stimulation of the growth of human heteroploid HeLa cells. Isolated beta-oestradiol significantly inhibited the growth of HeLa cells.

Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1

Proceedings of the National Academy of Sciences, 2007

Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regu... more Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express α-gustducin. Ingestion of glucose by α-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from α-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses α-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for α-gustducin....

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T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1

Proceedings of the National Academy of Sciences, 2007

Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodiu... more Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or α-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 up-regulation. Gut-expressed taste signalin...

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Involvement of T1R3 in calcium-magnesium taste

Physiological Genomics, 2008

Calcium and magnesium are essential for survival but it is unknown how animals detect and consume... more Calcium and magnesium are essential for survival but it is unknown how animals detect and consume enough of these minerals to meet their needs. To investigate this, we exploited the PWK/PhJ (PWK) strain of mice, which, in contrast to the C57BL/6J (B6) and other inbred strains, displays strong preferences for calcium solutions. We found that the PWK strain also has strong preferences for MgCl2 and saccharin solutions but not representative salty, sour, bitter, or umami taste compounds. A genome scan of B6 × PWK F2 mice linked a component of the strain difference in calcium and magnesium preference to distal chromosome 4. The taste receptor gene, Tas1r3, was implicated by studies with 129.B6ByJ- Tas1r3 congenic and Tas1r3 knockout mice. Most notably, calcium and magnesium solutions that were avoided by wild-type B6 mice were preferred (relative to water) by B6 mice null for the Tas1r3 gene. Oral calcium elicited less electrophysiological activity in the chorda tympani nerve of Tas1r3 ...

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Trpm5 Null Mice Respond to Bitter, Sweet, and Umami Compounds

Chemical Senses, 2005

Trpm5 is a calcium-activated cation channel expressed selectively in taste receptor cells. A prev... more Trpm5 is a calcium-activated cation channel expressed selectively in taste receptor cells. A previous study reported that mice with an internal deletion of Trpm5, lacking exons 15-19 encoding transmembrane segments 1-5, showed no taste-mediated responses to bitter, sweet, and umami compounds. We independently generated knockout mice null for Trpm5 protein expression due to deletion of Trpm5#s promoter region and exons 1-4 (including the translation start site). We examined the tastemediated responses of Trpm5 null mice and wild-type (WT) mice using three procedures: gustatory nerve recording [chorda tympani (CT) and glossopharyngeal (NG) nerves], initial lick responses, and 24-h two-bottle preference tests. With bitter compounds, the Trpm5 null mice showed reduced, but not abolished, avoidance (as indicated by licking responses and preference ratios higher than those of WT), a normal CT response, and a greatly diminished NG response. With sweet compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, and absent or greatly reduced nerve responses. With umami compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, a normal NG response, and a greatly diminished CT response. Our results demonstrate that the consequences of eliminating Trmp5 expression vary depending upon the taste quality and the lingual taste field examined. Thus, while Trpm5 is an important factor in many taste responses, its absence does not eliminate all taste responses. We conclude that Trpm5-dependent and Trpm5-independent pathways underlie bitter, sweet, and umami tastes.

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[Determination of paternity using DNA analysis of chorionic villi]

Casopis lekaru ceskych, 1990

Using probes recognizing hypervariable regions in human DNA high precision paternity testing can ... more Using probes recognizing hypervariable regions in human DNA high precision paternity testing can be provided even in the first trimester of pregnancy. Paternity tests were performed in 14 families using DNA isolated from chorionic villi. The results indicate that by a single probe confirmation or exclusion of paternity from a DNA sample of chorionic villi the 1st trimester of pregnancy can be performed with a probability more than 99.99%.

Autonomous growth in serum-free medium and production of hepatocellular carcinomas by differentiated hepatocyte lines that overexpress transforming growth factor alpha 1

Cancer research, 1994

Transforming growth factor alpha (TGF-alpha) is a polypeptide closely associated with hepatocyte ... more Transforming growth factor alpha (TGF-alpha) is a polypeptide closely associated with hepatocyte proliferation in vivo and in vitro. In order to investigate the mechanisms by which TGF-alpha contributes to hepatocyte replication and transformation, we isolated hepatocytes from mice bearing a human TGF-alpha transgene and examined their growth properties and gene expression in defined, serum-free culture. The transgenic hepatocytes continued to overexpress human TGF-alpha mRNA and peptide, and were able to proliferate without exogenous growth factors in primary culture, in contrast to nontransgenic mouse hepatocytes. In short-term culture the transgenic hepatocytes underwent 1 wave of DNA replication at 72-96 h in culture before senescing, similar to nontransgenic hepatocytes supplemented with epidermal growth factor. Constitutive expression of TGF-alpha rendered the transgenic hepatocytes unresponsive to further growth stimulation by exogenous TGF-alpha, as well as other mitogens su...

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Heart infarction-like effect induced by natural catecholamines in vitro

Experimentelle Pathologie

Isolated rat hearts were perfused using retrograde technique under constant perfusion pressure or... more Isolated rat hearts were perfused using retrograde technique under constant perfusion pressure or under constant coronary flow. The addition of L-epinephrine or L-nor-epinephrine (1 microgram per ml) into the perfusion medium for one hour caused visible and irreversible morphological changes. They became apparent usually after 4 hours of perfusion in the form of small, pale, opaque spots of streaks gradually enlarging on the surface or on the transverse section of myocardium. Light microscope and electron microscope examination showed the disintegration process analogous to myocardial infarction but lacking the infiltration with blood elements. The structural changes were preceeded by increased release of lactate dehydrogenase into the effluent, the most characteristic metabolic change a accompanying myocardial injury. Although the underlying mechanism of cardiotoxic action catecholamines remains to be clarified, several factors under consideration could be eliminated like hyperlipi...

Heart infarction-like effect induced by natural catecholamines in vitro

Solitary Chemosensory Cells (SCCs) in the Pancreas

CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

Journal of Neuroscience, 2011

Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantl... more Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantly in the developing brain. To examine the in vivo function of CRMP5, we generated crmp5-deficient (crmp5 Ϫ/Ϫ) mice. Anti-calbindin immunofluorescence studies of crmp5 Ϫ/Ϫ mice revealed aberrant dendrite morphology; specifically, a decrease in the size of soma and diameter of primary dendrite of the cerebellar Purkinje cells at postnatal day 21 (P21) and P28, but not at P14. Coincidentally, CRMP5 is detected in Purkinje cells at P21 and P28 from crmp5 ϩ/Ϫ mice. In cerebellar slices of crmp5 Ϫ/Ϫ mice, the induction of long-term depression of excitatory synaptic transmission between parallel fibers and Purkinje cells was deficient. Given that brain-derived neurotrophic factor (BDNF) plays major roles in dendritic development, we tried to elucidate the possible roles of CRMP5 in BDNF signaling. The effect of BDNF to induce dendritic branching was markedly attenuated in cultured crmp5 Ϫ/Ϫ neurons. Furthermore, CRMP5 was tyrosine phosphorylated when coexpressed with neurotrophic tyrosine kinase receptor type 2 (TrkB), a receptor for BDNF, in HEK293T cells. These findings suggest that CRMP5 is involved in the development, maintenance and synaptic plasticity of Purkinje cells.

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$Research paper thumbnail of Hypothalamic gene expression in reproductively photoresponsive and photorefractory Siberian hamsters$

Hypothalamic gene expression in reproductively photoresponsive and photorefractory Siberian hamsters

Proceedings of the National Academy of Sciences, 2002

An interval timing mechanism in the brain governs reproduction in seasonally breeding mammals by ... more An interval timing mechanism in the brain governs reproduction in seasonally breeding mammals by triggering refractoriness to inhibitory short photoperiods during midwinter. The neural mechanisms responsible for the timing and induction of photorefractoriness by this seasonal clock are unknown. Using cDNA microarrays and RT-PCR, we identified a class of genes encoding thyroxine (T4)-binding proteins (transthyretin, T4-binding globulin, albumin) whose expression is associated with reproductive refractoriness to short day lengths. Down-regulation of these genes was associated with reduced hypothalamic T4 uptake, which was reversed by long-day photoperiod treatments that restored responsiveness to short days. Circulating T4 concentrations did not vary with states of photoresponsiveness in euthyroid hamsters, but blockade of thyroid function accelerated the onset of photorefractoriness to short days. These data link changes in gene expression in the hypothalamus to the functional output of a seasonal clock. Reproductive inhibition in short days depends on T4 only late in the nonbreeding season. Down-regulation of genes encoding T4-binding proteins in the hypothalamus during this interval may restrict access of a static T4 signal to hypothalamic target tissues that regulate reproduction, thereby timing annual transitions in reproductive function. Hypothalamic autoregulation of T4 influx may constitute a critical cellular process involved in the generation and expression of seasonal reproductive rhythms and suggests a previously undescribed mechanism by which neural targets gain access to peripheral hormones.

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Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase

Proceedings of the National Academy of Sciences, 1992

A mouse cDNA encoding a non-receptor-type phosphotyrosine phosphatase (PTP; EC 3.1.3.48) has been... more A mouse cDNA encoding a non-receptor-type phosphotyrosine phosphatase (PTP; EC 3.1.3.48) has been isolated. The 1570-base-pair cDNA contains a single open reading frame that predicts a 382-amino acid protein with Mr 44,640. The nucleic acid and amino acid sequences are homologous to those of a previously described human T-cell PTP [Cool, D.

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Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Proceedings of the National Academy of Sciences, 2013

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Determination of Singlet Oxygen Production and Antibacterial Effect of Nonpolar Porphyrins In Heterogeneous Systems

Analytical Letters, 2000

The possibility of using the iodide method and the method of bleaching of 4-nitroso-N, N&amp;... more The possibility of using the iodide method and the method of bleaching of 4-nitroso-N, N&amp;amp;amp;amp;amp;amp;amp;amp;#39;-dimethylaniline, developed originally for homogeneous aqueous medium for the determination of singlet oxygen production, was tested for water-insoluble nonpolar senzitizers adsorbed on the silica gel support. Sensitizers of the porphyrin and metalloporphyrin type (tetraphenylporphin (TPP), protoporphyrin IX (PPIX), tetra(4-nitrophenyl)porphin (TPP(NO2)4 and complexes of TPP with some

REVIEW ARTICLE-IMMUNOBIOLOGY-Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies

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