Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction

Geibel, John P.; Sritharan, Kumudesh C.; Geibel, Rainer; Geibel, Peter; Persing, John; Seeger, Achim; Roepke, Torsten K.; Deichstetter, Markus; Prinz, Christian; Cheng, Sam X.; Martin, David P.; Hebert, Steven C.

doi:10.1073/pnas.0602996103

Cited by 119 publications

(141 citation statements)

References 51 publications

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“…To determine whether the CaR might regulate PTHrP production by breast cells in a similar fashion, we treated cells with the isoformnonspecific phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), to see if this would block the ability of high calcium to modulate cAMP and PTHrP production in MMECs and Comma-D cells (7). As expected (Fig.…”

Section: Volume 283 • Number 36 • September 5 2008mentioning

confidence: 73%

“…CaR Regulates cAMP Production, Not Degradation-In intestinal epithelial cells, activation of the CaR lowers cAMP levels by stimulating phosphodiesterase activity (7). To determine whether the CaR might regulate PTHrP production by breast cells in a similar fashion, we treated cells with the isoformnonspecific phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), to see if this would block the ability of high calcium to modulate cAMP and PTHrP production in MMECs and Comma-D cells (7).…”

Section: Volume 283 • Number 36 • September 5 2008mentioning

confidence: 99%

“…Instead, we hypothesized that activation of the CaR altered cAMP production. If this were the case, we reasoned that maximal stimulation of adenylyl cyclase activity with CTX (7,46) should block the ability of high calcium to change cAMP levels or PTHrP production in either cell type. As shown in Fig.…”

Section: Volume 283 • Number 36 • September 5 2008mentioning

confidence: 99%

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Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Mamillapalli

VanHouten

Zawalich

et al. 2008

Journal of Biological Chemistry

129

113

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The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that signals in response to extracellular calcium and regulates parathyroid hormone secretion. The CaR is also expressed on normal mammary epithelial cells (MMECs), where it has been shown to inhibit secretion of parathyroid hormone-related protein (PTHrP) and participate in the regulation of calcium and bone metabolism during lactation. In contrast to normal breast cells, the CaR has been reported to stimulate PTHrP production by breast cancer cells. In this study, we confirmed

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Section: Volume 283 • Number 36 • September 5 2008mentioning

confidence: 73%

Section: Volume 283 • Number 36 • September 5 2008mentioning

confidence: 99%

See 1 more Smart Citation

Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Mamillapalli

VanHouten

Zawalich

et al. 2008

Journal of Biological Chemistry

129

113

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“…The administration of calcimimetics to patients with chronic kidney disease (CKD) before the stage of dialysis, however, may lead to increased urinary calcium excretion and phosphate retention via direct effects on the kidney and indirect effects through inhibition of PTH. Recently, the group of the late Steve Hebert showed that modulation of intestinal CaR activity by calcimimetics leads to a reduction of excessive fluid secretion into the gut lumen upon stimulation by cAMP-and cGMP-dependent secretagogues (16). Calcimimetics could thus represent a new tool in the control of cholera toxin-and Escherichia coli endotoxin-induced diarrhea.…”

Section: Development Of Calcimimetics and Calcilyticsmentioning

confidence: 99%

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Drüeke¹,

Ritz²

2009

Clinical Journal of the American Society of Nephrology

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The discovery of the calcium-sensing receptor (CaR) 15 yr ago was rapidly followed by the development of drugs modulating its activity, the so-called calcimimetics (increasing the CaR signal) and calcilytics (decreasing the CaR signal). The indication for calcimimetics is treatment of primary and secondary hyperparathyroidism, whereas calcilytics have potential for treatment of osteoporosis. A large number of clinical studies has shown that cinacalcet, the only presently available calcimimetic, effectively reduces serum parathyroid hormone in dialysis patients with secondary hyperparathyroidism. In contrast to the effect of active vitamin D derivatives, it simultaneously decreases serum calcium and phosphorus. Experimental studies showed a concomitant decrease in parathyroid hyperplasia. In the treatment of secondary hyperparathyroidism of dialysis patients, important questions remain unresolved, for example, whether there are reasons to prefer calcimimetics to active vitamin D derivatives and whether combined administration offers advantages compared with calcimimetics or active vitamin D given in isolation. For lowering parathyroid hormone, available evidence from recent studies suggests that combination therapy should be preferred to single drug treatment because of less side-effects and greater efficacy in controlling parathyroid overfunction. Future randomized controlled trial must answer whether calcimimetics impact on cardiovascular events or survival and whether in this respect there are differences between vitamin D sterols and calcimimetics.

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“…The hope is that a clinically useful inhibitor of the CFTR channel could eventually become an adjunct to the management of cholera (27), but no suitable inhibitor has yet been developed. A second approach shown to be effective in experimental animals is activation of the calcium-sensing receptor, which hastens breakdown of cAMP and thereby decreases the stimulation of secretory channels in intestinal epithelial cells (33). Other Bacterial Diarrheas.…”

Section: Diarrheamentioning

confidence: 99%

Acid-Base Disturbances in Gastrointestinal Disease

Gennari¹,

Weise²

2008

Clinical Journal of the American Society of Nephrology

141

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Disruption of normal gastrointestinal function as a result of infection, hereditary or acquired diseases, or complications of surgical procedures uncovers its important role in acid-base homeostasis. Metabolic acidosis or alkalosis may occur, depending on the nature and volume of the unregulated losses that occur. Investigation into the specific pathophysiology of gastrointestinal disorders has provided important new insights into the normal physiology of ion transport along the gut and has also provided new avenues for treatment. This review provides a brief overview of normal ion transport along the gut and then discusses the pathophysiology and treatment of the metabolic acid-base disorders that occur when normal gut function is disrupted.

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Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction

Cited by 119 publications

References 51 publications

Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Acid-Base Disturbances in Gastrointestinal Disease

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