Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep: a potential contributory factor to postburn hypocalcemia.
OBJECTIVE
To test the hypothesis that the hypocalcemia and hypoparathyroidism that follow severe burn injury are related to up-regulation of the parathyroid gland calcium-sensing receptor (CaR), which may reduce the set-point for suppression of circulating parathyroid hormone by blood calcium.


METHODS
A controlled but unblinded study.


METHODS
An investigational intensive care unit.


METHODS
Female range ewes.


METHODS
Sheep were subjected to a 40% total body surface area burn under anesthesia (n = 9) or sham burn receiving anesthesia and fluid resuscitation only (n = 8) and were killed 48 hrs postburn.


RESULTS
Blood ionized calcium, magnesium, and creatinine, and urinary calcium, magnesium, and creatinine were monitored for 48 hrs. After the sheep were killed, parathyroids (burn group, n = 3; sham group, n = 4) and kidneys (n = 4, each group) were harvested, snap frozen in liquid nitrogen, and analyzed for CaR messenger ribonucleic acid (mRNA) by Northern blot, and were analyzed for CaR cell-surface staining by immunocytochemistry with a polyclonal CaR-specific antiserum (parathyroids only). Bumed sheep were hypocalcemic and hypomagnesemic compared with sham-burned control sheep. CaR mRNA was increased by 50% (p < 0.005, analysis of variance) with a corresponding increase in the intensity of CaR immunoreactivity associated with the cell surface in parathyroids obtained from burned (n = 3) compared with sham-burned (n = 2) sheep. These findings are consistent with up-regulation of the parathyroid CaR and a related decrease in set-point for calcium suppression of parathyroid hormone secretion that may contribute to the previously reported postburn hypoparathyroidism and hypocalcemia.
Murphey
E D
ED
Department of Anesthesia, University of Texas Medical Branch and Shriners Burns Hospital, Galveston 77555-0362,  USA.
Chattopadhyay
N
N
Bai
M
M
Kifor
O
O
Harper
D
D
Traber
D L
DL
Hawkins
H K
HK
Brown
E M
EM
Klein
G L
GL
D000818:Animals; D015152:Blotting, Northern; D002056:Burns / Q000150:complications*; D002118:Calcium / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D005440:Fluid Therapy; D006996:Hypocalcemia / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007011:Hypoparathyroidism / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008275:Magnesium Deficiency / Q000209:etiology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology*; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D012307:Risk Factors; D012756:Sheep; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D002118:Calcium