期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 41, 页码 17791-17796出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1009078107
关键词
chemosensation; multimodal sensor; peptide hormone; calcilytic; calcimimetic
资金
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
- National Institutes of Health [P01-0707056]
The calcium-sensing receptor (CaR) is the major sensor and regulator of extracellular Ca2+, whose activity is allosterically regulated by amino acids and pH. Recently, CaR has been identified in the stomach and intestinal tract, where it has been proposed to function in a non-Ca2+ homeostatic capacity. Luminal nutrients, such as Ca2+ and amino acids, have been recognized for decades as potent stimulants for gastrin and acid secretion, although the molecular basis for their recognition remains unknown. The expression of CaR on gastrin-secreting G cells in the stomach and their shared activation by Ca2+, amino acids, and elevated pH suggest that CaR may function as the elusive physiologic sensor regulating gastrin and acid secretion. The genetic and pharmacologic studies presented here comparing CaR-null mice and wild-type littermates support this hypothesis. Gavage of Ca2+, peptone, phenylalanine, Hepes buffer (pH 7.4), and CaR-specific calcimimetic, cinacalcet, stimulated gastrin and acid secretion, whereas the calcilytic, NPS 2143, inhibited secretion only in the wild-type mouse. Consistent with known growth and developmental functions of CaR, G-cell number was progressively reduced between 30 and 90 d of age by more than 65% in CaR-null mice. These studies of nutrient-regulated G-cell gastrin secretion and growth provide definitive evidence that CaR functions as a physiologically relevant multimodal sensor. Medicinals targeting diseases of Ca2+ homeostasis should be reviewed for effects outside traditional Ca2+-regulating tissues in view of the broader distribution and function of CaR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据