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Record Details

Record 32 of 878
Extracellular calcium sensing and extracellular calcium signaling
Author and Affiliation:
Brown, E. M.(Brigham and Women's Hospital and Harvard Medical School, Endocrine-Hypertension Division, Department of Medicine, Boston, Massachusetts 02115, United States)
MacLeod, R. J.
O'Malley, B. W. [Principal Investigator]
Abstract: The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.
Publication Date: Jan 01, 2001
Document ID:
20040112621
(Acquired Oct 05, 2004)
Subject Category: LIFE SCIENCES (GENERAL)
Document Type: Journal Article
Publication Information: Physiological reviews; p. 239-297; (ISSN 0031-9333); Volume 81; 1
Publisher Information: United States
Contract/Grant/Task Num: DK-41415; DK-46422; DK-48330
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: CALCIUM; DETECTION; APOPTOSIS; CELL DIVISION; DIFFERENTIATION (BIOLOGY); GENE EXPRESSION REGULATION; GENETICS; HOMEOSTASIS; SIGNAL TRANSMISSION
Other Descriptors: CALCIUM SIGNALING/DRUG EFFECTS/PHYSIOLOGY; RECEPTORS, CELL SURFACE/GENETICS/METABOLISM; ALTERNATIVE SPLICING; ANIMALS; APOPTOSIS/PHYSIOLOGY; CELL DIFFERENTIATION/PHYSIOLOGY; CELL DIVISION/PHYSIOLOGY; GTP-BINDING PROTEINS/METABOLISM; GENE EXPRESSION REGULATION; HOMEOSTASIS/PHYSIOLOGY; HUMAN; ORGAN SPECIFICITY; POLYMORPHISM (GENETICS); RECEPTORS, CALCIUM-SENSING; SIGNAL TRANSDUCTION/PHYSIOLOGY; STRUCTURE-ACTIVITY RELATIONSHIP; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S; NASA DISCIPLINE MUSCULOSKELETAL; NON-NASA CENTER; REVIEW; REVIEW, TUTORIAL
Availability Source: Other Sources
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