J Huan1, G Martuseviciene, K Olgaard, E Lewin. 1. Nephrological Department P, Rigshospitalet and Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND: Plasma ionized calcium (p-Ca(2+)) is kept within a very narrow range and deviations are rapidly corrected by flux of Ca(2+) between extracellular fluid and the labile calcium pool at the quiescent bone surface. The calcium sensing at the bone surface represents a physiological interesting model for the rapid minute-to-minute regulation of p-Ca(2+). Our aim was to study whether the calcium-sensing receptor (CaR) has a role in the rapid recovery of p-Ca(2+) from acute induced hypocalcaemia. MATERIAL AND METHODS: Male Wistar rats were thyroparathyroidectomized (TPTX). Acute hypocalcaemia in the animals was induced by infusion of EGTA (40-50 mM EGTA, 3.0 mL h(-1) for 30 min). Thereafter the recovery of p-Ca(2+) was followed. Vehicle or the CaR activators, R-568 (2 mg as a bolus twice) or gentamycin were administrated intravenously. RESULTS: EGTA infusion resulted in significantly lower nadir of hypocalcaemia in R-568- or gentamycin-treated rats compared to vehicle-treated rats (P < 0.01). During recovery phase p-Ca(2+) remained significantly lower in R-568 rats (P < 0.001). As such p-Ca(2+) levels recovered to basal levels in the vehicle group within 70 min after stopping EGTA, while R-568 or gentamycin rats remained significantly hypocalcaemic. CONCLUSIONS: The CaR activators R-568 and gentamycin, both significantly delayed the recovery of p-Ca(2+) from acute EGTA-induced hypocalcaemia in TPTX rats. This novel finding suggests the existence of calcium sensing by bone of importance for the rapid minute-to-minute regulation of p-Ca(2+).
BACKGROUND: Plasma ionizedcalcium (p-Ca(2+)) is kept within a very narrow range and deviations are rapidly corrected by flux of Ca(2+) between extracellular fluid and the labile calcium pool at the quiescent bone surface. The calcium sensing at the bone surface represents a physiological interesting model for the rapid minute-to-minute regulation of p-Ca(2+). Our aim was to study whether the calcium-sensing receptor (CaR) has a role in the rapid recovery of p-Ca(2+) from acute induced hypocalcaemia. MATERIAL AND METHODS: Male Wistar rats were thyroparathyroidectomized (TPTX). Acute hypocalcaemia in the animals was induced by infusion of EGTA (40-50 mM EGTA, 3.0 mL h(-1) for 30 min). Thereafter the recovery of p-Ca(2+) was followed. Vehicle or the CaR activators, R-568 (2 mg as a bolus twice) or gentamycin were administrated intravenously. RESULTS:EGTA infusion resulted in significantly lower nadir of hypocalcaemia in R-568- or gentamycin-treated rats compared to vehicle-treated rats (P < 0.01). During recovery phase p-Ca(2+) remained significantly lower in R-568rats (P < 0.001). As such p-Ca(2+) levels recovered to basal levels in the vehicle group within 70 min after stopping EGTA, while R-568 or gentamycinrats remained significantly hypocalcaemic. CONCLUSIONS: The CaR activators R-568 and gentamycin, both significantly delayed the recovery of p-Ca(2+) from acute EGTA-induced hypocalcaemia in TPTXrats. This novel finding suggests the existence of calcium sensing by bone of importance for the rapid minute-to-minute regulation of p-Ca(2+).
Authors: Christopher Dedic; Tin Shing Hung; Alan M Shipley; Akira Maeda; Thomas Gardella; Andrew L Miller; Paola Divieti Pajevic; Joseph G Kunkel; Alessandro Rubinacci Journal: Bone Date: 2018-07-24 Impact factor: 4.398