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  • 2000-2004  (1)
  • 1995-1999  (1)
  • 1975-1979
  • Aging effects  (1)
  • Intracellular Ca2+  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Clinical and experimental nephrology 4 (2000), S. 293-299 
    ISSN: 1437-7799
    Keywords: Key words Calcium receptor ; HEK293 ; NPS R-568 ; Calcimimetics ; Intracellular Ca2+
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The Ca2+ receptor (CaR) plays a key role in maintaining Ca2+ homeostasis by its presence in the parathyroid gland and kidney. NPS R-568 (referred to as KRN568 in Japan) is a phenylalkylamine compound that activates the CaR. It has been difficult to study Ca2+-sensing mechanisms because of the lack of cell model systems that express reasonable numbers of CaR coupled to downstream effectors and physiological responses. This study was conducted to evaluate the effects of NPS R-568 on the CaR both in vitro and in vivo. Methods. Western blotting analysis of CaR was performed to confirm the existence of CaR in human embryonic kidney 293 (HEK293) cells expressing human CaR (HuCaR-HEK293). Intracellular Ca2+ concentration ([Ca2+]i) and inositol trisphosphate (IP3) content were measured in HuCaR-HEK293 after the addition of NPS R-568 and other agonists. Male Sprague-Dawley rats received NPS R-568 orally, and plasma Ca2+ levels and serum parathyroid hormone (PTH) levels were determined. Results. Western blotting analysis of the crude plasma membrane fraction prepared from HuCaR-HEK293 identified bands immunoreactive with a human CaR-specific antibody. NPS R-568 dose-dependently and stereoselectively increased [Ca2+]i in HuCaR-HEK293, whereas NPS R-568 had no effects in wild-type HEK293 cells. These effects of NPS R-568 were associated with an increase in cytoplasmic IP3 levels and were abolished in the absence of extracellular Ca2+. Single oral administration of NPS R-568 suppressed PTH secretion, followed by decreased plasma Ca2+ levels, in normal rats. Conclusions. These results suggest that NPS R-568 activates CaR and suppresses PTH secretion in vitro and in vivo.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European archives of oto-rhino-laryngology and head & neck 254 (1997), S. 145-149 
    ISSN: 1434-4726
    Keywords: Eighth nerve compound action potential ; Aging effects ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The eighth nerve compound action potential (CAP) in 95 guinea pigs was measured using click stimuli to investigate age-related changes in their neural auditory thresholds. The animals were separated into three groups: group A (n = 43, 86 ears; 2–4 months old); group B (n = 29; 58 ears, 13–15 months old); and group C (n = 23; 46 ears, 23–25 months old). With increasing age, a gradual elevation of CAP thresholds was clearly seen among the three groups. The negative peak (N1) latencies of the CAP were prolonged, and the N1 amplitudes of the CAP decreased. There were significant differences in N1 latencies among the three groups and in N1 amplitudes between groups A and B, and between groups A and C. However, the rate of decline of the thresholds as well as the input-output function curves of the CAP varied in some of the oldest animals, suggesting that there were some individual differences in degenerative aging processes of the auditory system.
    Type of Medium: Electronic Resource
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