The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.

Renal dopamine D1-like receptors (D1R and D5R) and the gastrin receptor (CCKBR) are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other\u27s expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D5R and CCKBR and in RPT cells from a male normotensive human. The specificity of D5R in the D5R and CCKBR interaction was verified further using a selective D5R antagonist, LE-PM436. Also, D5R and CCKBR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCKBR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs) is greater in D5R-/- mice than D5R+/+ littermates and D5R protein expression in PMFs is also greater in CCKBR-/- mice than CCKBR+/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCKBR and D5R proteins in PMFs. Disruption of CCKBR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCKBR antagonist and Sch23390, a D1R/D5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by Sch23390 while the natriuresis caused by fenoldopam, a D1R/D5R agonist, was blocked by YF476. Taken together, our findings indicate that CCKBR and D5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake

Relationships, variety & synergy:the vital ingredients for scholarship in engineering education? A case study

This paper begins with the argument that within modern-day society, engineering has shifted from being the scientific and technical mainstay of industrial, and more recently digital change to become the most vital driver of future advancement. In order to meet the inevitable challenges resulting from this role, the nature of engineering education is constantly evolving and as such engineering education has to change. The paper argues that what is needed is a fresh approach to engineering education – one that is sufficiently flexible so as to capture the fast-changing needs of engineering education as a discipline, whilst being pedagogically suitable for use with a range of engineering epistemologies. It provides an overview of a case study in which a new approach to engineering education has been developed and evaluated. The approach, which is based on the concept of scholarship, is described in detail. This is followed by a discussion of how the approach has been put into practice and evaluated. The paper concludes by arguing that within today's market-driven university world, the need for effective learning and teaching practice, based in good scholarship, is fundamental to student success

Automation: Survival Tools for the Hospital Laboratory

New technologies based on manufacturing automation are now making hospital clinical laboratories into profit centers. Ever since the Japanese introduced the laboratory robotics and automation paradigm in the early 1980s, over 20 laboratories in North America and Europe have installed fully functional robotic systems

The renal dopaminergic system: Novel diagnostic and therapeutic approaches in hypertension and kidney disease

© 2015 Elsevier Inc. All rights reserved. Salt sensitivity of blood pressure, whether in hypertensive or normotensive subjects, is associated with increased cardiovascular risk and overall mortality. Salt sensitivity can be treated by reducing NaCl consumption. However, decreasing salt intake in some may actually increase cardiovascular risk, including an increase in blood pressure, that is, inverse salt sensitivity. Several genes have been associated with salt sensitivity and inverse salt sensitivity. Some of these genes encode proteins expressed in the kidney that are needed to excrete a sodium load, for example, dopamine receptors and their regulators, G protein-coupled receptor kinase 4 (GRK4). We review here research in this field that has provided several translational opportunities, ranging from diagnostic tests to gene therapy, such as (1) a test in renal proximal tubule cells isolated from the urine of humans that may determine the salt-sensitive phenotype by analyzing the recruitment of dopamine D1 receptors to the plasma membrane; (2) the presence of common GRK4 gene variants that are not only associated with hypertension but may also be predictive of the response to antihypertensive therapy; (3) genetic testing for polymorphisms of the dopamine D2 receptor that may be associated with hypertension and inverse salt sensitivity and may increase the susceptibility to chronic kidney disease because of loss of the antioxidant and anti-inflammatory effects of the renal dopamine D2 receptor, and (4) in vivo renal selective amelioration of renal tubular genetic defects by a gene transfer approach, using adeno-associated viral vectors introduced to the kidney by retrograde ureteral infusion

The importance of the gastrorenal axis in the control of body sodium homeostasis

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