Chronic calcitonin administration and renal calcium transport in the rat.
1. While calcitonin (CT) has now been clearly demonstrated to be a renal Ca2+-conserving hormone and may share similar transport mechanisms with parathyroid hormone (PTH), the effect of prolonged CT exposure on renal Ca2+ transport has not been evaluated. 2. Consequently, a submaximal and maximal Ca2+-conserving concentration of human CT was infused into groups of anaesthetized acutely thyroparathyroidectomized rats that had been treated with twice daily subcutaneous human (h) CT at a low or high dose or vehicle for 12 days. 3. The maximal hCT infusion (10 microg bolus and per hour) produced a marked inhibitory effect on renal Ca2+ excretion in vehicle-treated rats, with the fractional excretion rate of Ca2+ being reduced from 4.49+/-0.31 to 139+/-0.23% (P<0.001). However, in rats pretreated with high concentrations of hormone (0.25 microg hCT) twice daily for 12 days, marked Ca2+ conservation was measured (fractional excretion 1.09+/-0.18%), which was not altered by the additional intravenous administration of maximal hCT. 4. Renal Mg2+ transport was similarly altered by hCT administration, without any evidence that prolonged CT inhibited renal Mg2+ transport. The increase in glomerular filtration rate caused by hCT also appeared to persist with repeated hormone administration. The fractional excretion of Na+ and PO4 was significantly increased by high- but not low-dose hCT treatment and was not altered by the addition of a maximal hormone dose at day 12. 5. The present study failed to demonstrate any down-regulation of the response to prolonged hCT administration when renal Ca2+ and Mg2+ transport was measured. If renal escape does occur with CT, as has been suggested but not proven with PTH, other mechanisms, such as hormone production or release, may be responsible.
Carney
S L
SL
Discipline of Medicine, Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Thompson
L
L
D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D017136:Ion Transport / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
D010710:Phosphates; D002116:Calcitonin; D012964:Sodium; D008274:Magnesium; D002118:Calcium