Ed. Murphey et al., Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep: A potential contributory factor to postburn hypocalcemia, CRIT CARE M, 28(12), 2000, pp. 3885-3890
Objective: To test the hypothesis that the hypocalcemia and hypoparathyroid
ism that follow severe burn injury are related to up-regulation of the para
thyroid gland calcium-sensing receptor (CaR), which may reduce the set-poin
t for suppression of circulating parathyroid hormone by blood calcium.
Design: A controlled but unblinded study.
Setting: An investigational intensive care unit,
Subjects: Female range ewes.
Intervention: Sheep were subjected to a 40% total body surface area burn un
der anesthesia (n = 9) or sham burn receiving anesthesia and fluid resuscit
ation only (n = 8) and were killed 48 hrs postburn,
Measurements and 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 Northe
rn blot, and were analyzed far Cap cell-surface staining by immunocytochemi
stry with a polyclonal CaR-specific antiserum (parathyroids only). Burned s
heep were hypocalcemic and hypomagnesemic compared with sham-burned control
sheep. Cap mRNA was increased by 50% (p < 0.005, analysis of variance) wit
h a corresponding increase in the intensity of CaR immunoreactivity associa
ted with the cell surface in parathyroids obtained from burned (n = 3) comp
ared 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 c
alcium suppression of parathyroid hormone secretion that may contribute to
the previously reported postburn hypoparathyroidism and hypocalcemia.