Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep: A potential contributory factor to postburn hypocalcemia

E. D. Murphey, Naibedya Chattopadhyay, Mei Bai, Olga Kifor, Donald Harper, Daniel L. Traber, Hal K. Hawkins, Edward M. Brown, Gordon L. Klein

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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. 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 under anesthesia (n = 9) or sham burn receiving anesthesia and fluid resuscitation 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 Northern blot, and were analyzed for CaR cell-surface staining by immunocytochemistry with a polyclonal CaR-specific antiserum (parathyroids only). Burned 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.

Original languageEnglish (US)
Pages (from-to)3885-3890
Number of pages6
JournalCritical Care Medicine
Volume28
Issue number12
StatePublished - 2000

Fingerprint

Calcium-Sensing Receptors
Hypocalcemia
Sheep
Up-Regulation
Wounds and Injuries
Calcium
Hypoparathyroidism
Parathyroid Hormone
Magnesium
Creatinine
Anesthesia
RNA
Parathyroid Glands
Body Surface Area
Resuscitation
Northern Blotting
Intensive Care Units
Immune Sera
Analysis of Variance
Nitrogen

Keywords

  • Burns
  • Calcium-sensing receptor
  • Hypocalcemia
  • Hypoparathyroidism
  • Interleukin-1
  • Interleukin-6
  • Kidney
  • Magnesium depletion
  • Parathyroid glands
  • Sheep

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Murphey, E. D., Chattopadhyay, N., Bai, M., Kifor, O., Harper, D., Traber, D. L., ... Klein, G. L. (2000). Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep: A potential contributory factor to postburn hypocalcemia. Critical Care Medicine, 28(12), 3885-3890.

Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep : A potential contributory factor to postburn hypocalcemia. / Murphey, E. D.; Chattopadhyay, Naibedya; Bai, Mei; Kifor, Olga; Harper, Donald; Traber, Daniel L.; Hawkins, Hal K.; Brown, Edward M.; Klein, Gordon L.

In: Critical Care Medicine, Vol. 28, No. 12, 2000, p. 3885-3890.

Research output: Contribution to journalArticle

Murphey, ED, Chattopadhyay, N, Bai, M, Kifor, O, Harper, D, Traber, DL, Hawkins, HK, Brown, EM & Klein, GL 2000, 'Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep: A potential contributory factor to postburn hypocalcemia', Critical Care Medicine, vol. 28, no. 12, pp. 3885-3890.
Murphey, E. D. ; Chattopadhyay, Naibedya ; Bai, Mei ; Kifor, Olga ; Harper, Donald ; Traber, Daniel L. ; Hawkins, Hal K. ; Brown, Edward M. ; Klein, Gordon L. / Up-regulation of the parathyroid calcium-sensing receptor after burn injury in sheep : A potential contributory factor to postburn hypocalcemia. In: Critical Care Medicine. 2000 ; Vol. 28, No. 12. pp. 3885-3890.
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abstract = "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. 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 under anesthesia (n = 9) or sham burn receiving anesthesia and fluid resuscitation 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 Northern blot, and were analyzed for CaR cell-surface staining by immunocytochemistry with a polyclonal CaR-specific antiserum (parathyroids only). Burned 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.",
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AU - Chattopadhyay, Naibedya

AU - Bai, Mei

AU - Kifor, Olga

AU - Harper, Donald

AU - Traber, Daniel L.

AU - Hawkins, Hal K.

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AB - 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. 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 under anesthesia (n = 9) or sham burn receiving anesthesia and fluid resuscitation 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 Northern blot, and were analyzed for CaR cell-surface staining by immunocytochemistry with a polyclonal CaR-specific antiserum (parathyroids only). Burned 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.

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