5 results on '"Chow, Billy K. C."'
Search Results
2. Secretin is involved in sodium conservation through the renin-angiotensin-aldosterone system.
- Author
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Juan Bai and Chow, Billy K. C.
- Abstract
Secretin (SCT) and its receptor (SCTR) are important in fluid regulation at multiple levels via the modulation of expression and translocation of renal aquaporin 2 and functions of central angiotensin II (ANGII). The functional interaction of SCT with peripheral ANGII, however, remains unknown. As the ANGII-aldosterone axis dominates the regulation of renal epithelial sodium channel (ENaC) function, we therefore tested whether SCT/SCTR can regulate sodium homeostasis via the renin-angiotensin-aldosterone system. SCTR-knockout (SCTR-/-) mice showed impaired aldosterone synthase (CYP11B2) expression and, consequently, aldosterone release upon intraperitoneal injection of ANGII. Endogenous ANGII production induced by dietary sodium restriction was higher in SCTR-/- than in C57BL/6N [wild-type (WT)] mice, but CYP11B2 and aldosterone synthesis were not elevated. Reduced accumulation of cholesteryl ester--the precursor of aldosterone--was observed in adrenal glands of SCTR-/- mice that were fed a low-sodium diet. Absence of SCTR resulted in elevated basal transcript levels of adrenal CYP11B2 and renal ENaCs. Although transcript and protein levels of ENaCs were similar in WT and SCTR-/- mice under sodium restriction, ENaCs in SCTR-/- mice were less sensitive to amiloride hydrochloride. In summary, the SCT/SCTR axis is involved in aldosterone precursor uptake, and the knockout of SCTR results in defective aldosterone biosynthesis/release and altered sensitivity of ENaCs to amiloride.--Bai, J., Chow, B. K. C. Secretin is involved in sodium conservation through the renin-angiotensin-aldosterone system. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
3. Secretin receptor-knockout mice are resistant to high-fat diet-induced obesity and exhibit impaired intestinal lipid absorption.
- Author
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Sekar, Revathi and Chow, Billy K. C.
- Subjects
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GASTROINTESTINAL diseases , *GASTROINTESTINAL hormones , *PANCREATIC secretions , *LIPIDS , *GLUCOSE tolerance tests , *INSULIN resistance - Abstract
Secretin, a classical gastrointestinal hormone released from S cells in response to acid and dietary lipid, regulates pleiotropic physiological functions, such as exocrine pancreatic secretion and gastric motility. Subsequent to recently proposed revisit on secretin's metabolic effects, we have confirmed lipolytic actions of secretin during starvation and discovered a hormone-sensitive lipase-mediated mechanistic pathway behind. In this study, a 12 wk high-fat diet (HFD) feeding to secretin receptor-knockout (SCTR-/-) mice and their wild-type (SCTR+/+) litter-mates revealed that, despite similar food intake, SCTRT-/- mice gained significantly less weight (SCTR+/+: 49.6±0.9 g; SCTRT-/-: 44.7±1.4 g; P<0.05) and exhibited lower body fat content. These SCTRT-/- mice have corresponding alleviated HFD-associated hyperleptinemia and improved glucose/insulin tolerance. Further analyses indicate that SCTRT-/- have impaired intestinal fatty acid absorption while having similar energy expenditure and locomotor activity. Reduced fat absorption in the intestine is further supported by lowered postprandial triglyceride concentrations in circulation in SCTR-/- mice. In jejunal cells, transcript and protein levels of a key fat absorption regulator, cluster of differentiation 36 (CD36), was reduced in knockout mice, while transcript of Cd36 and fatty-acid uptake in isolated enterocytes was stimulated by secretin. Based on our findings, a novel positive feedback pathway involving secretin and CD36 to enhance intestinal lipid absorption is being proposed. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
4. Transmembrane peptides as unique tools to demonstrate the in vivo action of a cross-class GPCR heterocomplex.
- Author
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Lee, Leo T. O., Ng, Stephanie Y. L., Chu, Jessica Y. S., Sekar, Revathi, Harikumar, Kaleeckal G., Miller, Laurence J., and Chow, Billy K. C.
- Subjects
PHYSIOLOGICAL effects of angiotensins ,SECRETIN ,CYCLIC adenylic acid ,PEPTIDES ,MEMBRANE proteins - Abstract
Angiotensin (ANGII) and secretin (SCT) share overlapping, interdependent osmoregulatory functions in brain, where SCT peptide/receptor function is required for ANGII action, yet the molecular basis is unknown. Since receptors for these peptides (AT1aR, SCTR) are coexpressed in osmoregulatory centers, a possible mechanism is formation of a cross-class receptor heterocomplex. Here, we demonstrate such a complex and its functional importance to modulate signaling. Association of AT1aR with SCTR reduced ability of SCT to stimulate cyclic adenosine monophosphate (cAMP), with signaling augmented in presence of ANGII or constitutively active AT1aR. Several transmembrane (TM) peptides of these receptors were able to affect their conformation within complexes, reducing receptor BRET signals. AT1aR TM1 affected only formation and activity of the heterocomplex, without effect on homomers of either receptor, and reduced SCT-stimulated cAMP responses in cells expressing both receptors. This peptide was active in vivo by injection into mouse lateral ventricle, thereby suppressing water-drinking behavior after hyperosmotic shock, similar to SCTR knockouts. This supports the interpretation that active conformation of AT1aR is a key modulator of cAMP responses induced by SCT stimulation of SCTR. The SCTR/AT1aR complex is physiologically important, providing differential signaling to SCT in settings of hyperosmolality or food intake, modulated by differences in levels of ANGII. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
5. An indispensable role of secretin in mediating the osmoregulatory functions of angiotensin II.
- Author
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Lee, Vien H. Y., Lee, Leo T. O., Chu, Jessica Y. S., Lam, Ian P. Y., Siu, Francis K. Y., Vaudry, Hubert, and Chow, Billy K. C.
- Subjects
BIOLOGICAL research ,SECRETIN ,OSMOREGULATION ,ANGIOTENSIN II ,HOMEOSTASIS ,CIRCUMVENTRICULAR organs ,VASOPRESSIN - Abstract
Fluid balance is critical to life and hence is tightly controlled in the body. Angiotensin II (ANGII) one of the most important components of this regulatory system, is recognized as a dipsogenic hormone that stimulates vasopressin (VP) expression and release. However, detailed mechanisms regarding how ANGII brings about these changes are not fully understood. In the present study, we show initially that the osmoregulatory functions of secretin (SCT) in the brain are similar to those of ANGII in mice and, more important we discovered the role of SCT
-/- as the link between ANGII and its downstream effects. This was substantiated by the use of two knockout mice, SCTR-/- in , SCT-/- in which we show the absence of an intact SCT/secretin receptor (SCTR) axis resulted in and abolishment or much reduced ANGII osmoregulatory functions. By immunohistochemical staining and in situ hybridization, the proteins and transcripts of SCT an its receptor are found in the paraventricular nucleus (PVN) and lamina terminalis. We propose that SCT produced in the circumventricular organs is transported and released in the PVN to stimulate vasopressin expression and release. In summary, our findings identify SCT and SCTR as novel elements of the ANGII osmoregulatory pathway in maintaining fluid balance in the body. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
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