Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts

Frick, Kevin K.; Bushinsky, David A.

doi:10.1152/ajprenal.00136.2010

Cited by 20 publications

(19 citation statements)

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“…Our interest in elucidating a role for an acid sensor in the kidney has been based on the relatively high expression of the proton-sensing receptor GPR4 in the kidney and the responses of other members of the proton-sensing family of GPCR to a decrease in pH in various tissues [e.g., OGR1 in bone (36,37,55) and lung], TDAG8 in lung carcinoma (50), and GPR4 in blood vessels (106). We found that the deletion of GPR4 impairs net acid excretion in the kidney, and therefore a spontaneous non-gap metabolic acidosis develops (88).…”

Section: Discussionmentioning

confidence: 99%

“…Protonsensing receptors (GPR4, OGR1, TDAG8) constitute a small, unique family of G protein-coupled receptors that accept protons as ligands and are activated by protons in a physiological pH range to induce production of cAMP (GPR4 and TDAG8) or inositol 1,4,5-trisphosphate (IP 3 ; OGR1) in a pH-dependent manner (51,59). Recently this unique family of GPCRs has been linked to pH sensor function in a number of tissues and organs, including bone (36,37), developing blood vessels and endothelial cells (106), airway smooth muscle cells (79), kidney (23,88), and to pathological conditions such as cancer (17,26,53,86), ischemia, inflammation (20,27), and acid-base disturbances (23,63,88). Of the three receptors, only GPR4 is relatively abundant in the kidney.…”

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confidence: 99%

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Adaptation by the collecting duct to an exogenous acid load is blunted by deletion of the proton-sensing receptor GPR4

Sun

Stephens

DuBose

et al. 2015

American Journal of Physiology-Renal Physiology

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Adaptation by the collecting duct to an exogenous acid load is blunted by deletion of the proton-sensing receptor GPR4

Sun

Stephens

DuBose

et al. 2015

American Journal of Physiology-Renal Physiology

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“…72 The reduction in osteoblast activity may also reduce the gene expression of several matrix proteins such as COL1A, OPN, and MGP, which may contribute to increased osteoarthritis development. 71,[74][75][76] Two of the pH-sensing G protein-coupled receptors, GPR68 and GPR65, have been reported to sense acidosis in bone cells.…”

Section: Role For the Ph-sensing Gpcrs In The Skeletal Systemmentioning

confidence: 99%

Emerging roles for the pH-sensing G protein-coupled receptors in response to acidotic stress

Sanderlin¹,

Justus²,

Krewson³

et al. 2015

CHC

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Protons (hydrogen ions) are the simplest form of ions universally produced by cellular metabolism including aerobic respiration and glycolysis. Export of protons out of cells by a number of acid transporters is essential to maintain a stable intracellular pH that is critical for normal cell function. Acid products in the tissue interstitium are removed by blood perfusion and excreted from the body through the respiratory and renal systems. However, the pH homeostasis in tissues is frequently disrupted in many pathophysiologic conditions such as in ischemic tissues and tumors where protons are overproduced and blood perfusion is compromised. Consequently, accumulation of protons causes acidosis in the affected tissue. Although acidosis has profound effects on cell function and disease progression, little is known about the molecular mechanisms by which cells sense and respond to acidotic stress. Recently a family of pH-sensing G protein-coupled receptors (GPCRs), including GPR4, GPR65 (TDAG8), and GPR68 (OGR1), has been identified and characterized. These GPCRs can be activated by extracellular acidic pH through the protonation of histidine residues of the receptors. Upon activation by acidosis the pH-sensing GPCRs can transduce several downstream G protein pathways such as the G s , G q/11 , and G 12/13 pathways to regulate cell behavior. Studies have revealed the biological roles of the pH-sensing GPCRs in the immune, cardiovascular, respiratory, renal, skeletal, endocrine, and nervous systems, as well as the involvement of these receptors in a variety of pathological conditions such as cancer, inflammation, pain, and cardiovascular disease. As GPCRs are important drug targets, small molecule modulators of the pH-sensing GPCRs are being developed and evaluated for potential therapeutic applications in disease treatment.

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“…Chronic metabolic acidosis increases urine calcium without increasing intestinal calcium absorption resulting in bone calcium loss, acute by physicochemical dissolution, chronically by cell-mediated bone resorption (Frick and Bushinsky, 2010). This effect is independent of the nature of the metabolic acidosis.…”

Section: Calciummentioning

confidence: 99%

Scientific Opinion on the essential composition of total diet replacements for weight control

Products¹

2015

EFSA Journal

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Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the essential composition of total diet replacements for weight control. Total diet replacements for weight control are intended to induce a substantial energy deficit in overweight or obese adults who wish to lose weight and replace the whole diet in the context of energyrestricted diets for weight reduction. In this opinion, the Panel proposed a minimum protein content based on a Population Reference Intake for protein adjusted for the overweight or obese (75 g/day), a minimum carbohydrate content based on the obligatory glucose demands of the brain (30 g/day) and minimum contents of linoleic acid (11 g/day), α-linolenic acid (1.4 g/day) and micronutrients based on reference values established either by the Panel or by other scientific or authoritative bodies. Derived from the minimum content of macronutrients, the Panel proposed a minimum energy content of total diet replacements for weight control of 2 510 kJ/day (600 kcal/day). The Panel also advised on potential conditions and restrictions of use for these products. © European SUMMARYFollowing a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the essential composition of total diet replacements for weight control. Total diet replacements for weight control are intended to induce a substantial energy deficit in overweight or obese adults who wish to lose weight and replace the whole diet in the context of energy-restricted diets for weight reduction.The guiding principle for providing advice on the essential composition of total diet replacements for weight control should be that products are safe and suitable when consumed as a sole source of nutrition for several weeks to months by overweight or obese adults in the context of energy-restricted diets for weight reduction. In order to avoid nutrient deficiencies, these products should, therefore, provide at least the Population Reference Intake or the Adequate Intake for adults of all indispensable nutrients. As Dietary Reference Values are generally established for healthy, normal-weight individuals, specific consideration has been given by the Panel in this opinion whether there was an increase in nutrient requirements in the overweight or obese or (rapid) weight loss leads to an increased nutrient loss and thus a higher requirement. The Panel also considered the extent to which different diet compositions impact on losses in fat-free mass, and on other adverse effects of weight loss diets, such as gallstone formation. The effectiveness of a product in terms of extent of weight loss was not in itself considered an appropriate determinant for the necessary composition of total diet replacements for weight control. ProteinThe Population Reference Intake of 0.83 g/kg body weight per day cannot be directly applied to overweight or obese indi...

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Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts

Abstract: Frick KK, Bushinsky DA. Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts.

Cited by 20 publications

References 59 publications

Adaptation by the collecting duct to an exogenous acid load is blunted by deletion of the proton-sensing receptor GPR4

Adaptation by the collecting duct to an exogenous acid load is blunted by deletion of the proton-sensing receptor GPR4

Emerging roles for the pH-sensing G protein-coupled receptors in response to acidotic stress

Scientific Opinion on the essential composition of total diet replacements for weight control

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