Calcium-sensing receptor and recovery from hypocalcaemia in thyroparathyroidectomized rats.
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.


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+).
Huan
J
J
Nephrological Department P, Rigshospitalet and Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Martuseviciene
G
G
Olgaard
K
K
Lewin
E
E
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology; D006996:Hypocalcemia / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D016105:Parathyroidectomy; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000187:drug effects*; D013965:Thyroidectomy
D000931:Antidotes; D005839:Gentamicins; D044169:Receptors, Calcium-Sensing; D004533:Egtazic Acid