Aluminum is a weak agonist for the calcium-sensing receptor

Robert F. Spurney, Min Pi, Patrick Flannery, Leigh Quarles

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background. Aluminum (Al3+) has diverse biological effects mediated through activation of a putative extracellular cation-sensing receptor. A recently identified calcium-sensing receptor (CaSR), which has been identified in target tissues for Al3+, may transduce some of the biological effects of Al3+. Methods. To test this possibility, we transfected human embryonic kidney 293 (HEK 293) cells with a eDNA encoding the rat CaSR and evaluated CaSR expression by Western blot analysis and function by measurement of intracellular calcium ([Ca2+](i)) levels and inositol monophosphate (IP1) generation following stimulation with Al3+ and a panel of CaSR agonists. Results. The CaSR protein was detected by immunoblot analysis in cells transfected with the CaSR eDNA but not in nontransfected HEK 293 cells. In addition, [Ca2+](i) levels and IP1 generation were enhanced in a dose-dependent fashion by additions of the CaSR agonists calcium (Ca2+), magnesium (Mg2+), gadolinium (Gd3+), and neomycin only in cells transfected with CaSR. To determine if Al3+ activated CaSR, we stimulated cells transfected with rat CaSR with 10 μM to 1 mM concentrations of Al3+. Concentrations of Al3+ in the range of 10 μM to 100 μM had no effect on [Ca2+](i) levels or IP1 generation. In contrast, 1 mM Al3+ induced small but significant increases in both parameters. Whereas Gd3+ antagonized calcium-mediated activation of CaSR, pretreatment with Al13+ failed to block subsequent activation of rat CaSR by Ca2+, suggesting a distinct mechanism of Al3+ action. Conclusion. Al3+ is not a potent agonist for CaSR. Because Al3+ affects a variety of target tissues at micromolar concentrations, it seems unlikely that CaSR mediates these cellular actions of Al3+.

Original languageEnglish (US)
Pages (from-to)1750-1758
Number of pages9
JournalKidney International
Volume55
Issue number5
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Calcium-Sensing Receptors
Aluminum
Calcium
Kidney
Neomycin
Gadolinium
Inositol
Magnesium

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Aluminum is a weak agonist for the calcium-sensing receptor. / Spurney, Robert F.; Pi, Min; Flannery, Patrick; Quarles, Leigh.

In: Kidney International, Vol. 55, No. 5, 01.01.1999, p. 1750-1758.

Research output: Contribution to journalArticle

Spurney, Robert F. ; Pi, Min ; Flannery, Patrick ; Quarles, Leigh. / Aluminum is a weak agonist for the calcium-sensing receptor. In: Kidney International. 1999 ; Vol. 55, No. 5. pp. 1750-1758.
@article{bb8cb3a6b3684902810cc5be440fe4a7,
title = "Aluminum is a weak agonist for the calcium-sensing receptor",
abstract = "Background. Aluminum (Al3+) has diverse biological effects mediated through activation of a putative extracellular cation-sensing receptor. A recently identified calcium-sensing receptor (CaSR), which has been identified in target tissues for Al3+, may transduce some of the biological effects of Al3+. Methods. To test this possibility, we transfected human embryonic kidney 293 (HEK 293) cells with a eDNA encoding the rat CaSR and evaluated CaSR expression by Western blot analysis and function by measurement of intracellular calcium ([Ca2+](i)) levels and inositol monophosphate (IP1) generation following stimulation with Al3+ and a panel of CaSR agonists. Results. The CaSR protein was detected by immunoblot analysis in cells transfected with the CaSR eDNA but not in nontransfected HEK 293 cells. In addition, [Ca2+](i) levels and IP1 generation were enhanced in a dose-dependent fashion by additions of the CaSR agonists calcium (Ca2+), magnesium (Mg2+), gadolinium (Gd3+), and neomycin only in cells transfected with CaSR. To determine if Al3+ activated CaSR, we stimulated cells transfected with rat CaSR with 10 μM to 1 mM concentrations of Al3+. Concentrations of Al3+ in the range of 10 μM to 100 μM had no effect on [Ca2+](i) levels or IP1 generation. In contrast, 1 mM Al3+ induced small but significant increases in both parameters. Whereas Gd3+ antagonized calcium-mediated activation of CaSR, pretreatment with Al13+ failed to block subsequent activation of rat CaSR by Ca2+, suggesting a distinct mechanism of Al3+ action. Conclusion. Al3+ is not a potent agonist for CaSR. Because Al3+ affects a variety of target tissues at micromolar concentrations, it seems unlikely that CaSR mediates these cellular actions of Al3+.",
author = "Spurney, {Robert F.} and Min Pi and Patrick Flannery and Leigh Quarles",
year = "1999",
month = "1",
day = "1",
doi = "10.1046/j.1523-1755.1999.00432.x",
language = "English (US)",
volume = "55",
pages = "1750--1758",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Aluminum is a weak agonist for the calcium-sensing receptor

AU - Spurney, Robert F.

AU - Pi, Min

AU - Flannery, Patrick

AU - Quarles, Leigh

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Background. Aluminum (Al3+) has diverse biological effects mediated through activation of a putative extracellular cation-sensing receptor. A recently identified calcium-sensing receptor (CaSR), which has been identified in target tissues for Al3+, may transduce some of the biological effects of Al3+. Methods. To test this possibility, we transfected human embryonic kidney 293 (HEK 293) cells with a eDNA encoding the rat CaSR and evaluated CaSR expression by Western blot analysis and function by measurement of intracellular calcium ([Ca2+](i)) levels and inositol monophosphate (IP1) generation following stimulation with Al3+ and a panel of CaSR agonists. Results. The CaSR protein was detected by immunoblot analysis in cells transfected with the CaSR eDNA but not in nontransfected HEK 293 cells. In addition, [Ca2+](i) levels and IP1 generation were enhanced in a dose-dependent fashion by additions of the CaSR agonists calcium (Ca2+), magnesium (Mg2+), gadolinium (Gd3+), and neomycin only in cells transfected with CaSR. To determine if Al3+ activated CaSR, we stimulated cells transfected with rat CaSR with 10 μM to 1 mM concentrations of Al3+. Concentrations of Al3+ in the range of 10 μM to 100 μM had no effect on [Ca2+](i) levels or IP1 generation. In contrast, 1 mM Al3+ induced small but significant increases in both parameters. Whereas Gd3+ antagonized calcium-mediated activation of CaSR, pretreatment with Al13+ failed to block subsequent activation of rat CaSR by Ca2+, suggesting a distinct mechanism of Al3+ action. Conclusion. Al3+ is not a potent agonist for CaSR. Because Al3+ affects a variety of target tissues at micromolar concentrations, it seems unlikely that CaSR mediates these cellular actions of Al3+.

AB - Background. Aluminum (Al3+) has diverse biological effects mediated through activation of a putative extracellular cation-sensing receptor. A recently identified calcium-sensing receptor (CaSR), which has been identified in target tissues for Al3+, may transduce some of the biological effects of Al3+. Methods. To test this possibility, we transfected human embryonic kidney 293 (HEK 293) cells with a eDNA encoding the rat CaSR and evaluated CaSR expression by Western blot analysis and function by measurement of intracellular calcium ([Ca2+](i)) levels and inositol monophosphate (IP1) generation following stimulation with Al3+ and a panel of CaSR agonists. Results. The CaSR protein was detected by immunoblot analysis in cells transfected with the CaSR eDNA but not in nontransfected HEK 293 cells. In addition, [Ca2+](i) levels and IP1 generation were enhanced in a dose-dependent fashion by additions of the CaSR agonists calcium (Ca2+), magnesium (Mg2+), gadolinium (Gd3+), and neomycin only in cells transfected with CaSR. To determine if Al3+ activated CaSR, we stimulated cells transfected with rat CaSR with 10 μM to 1 mM concentrations of Al3+. Concentrations of Al3+ in the range of 10 μM to 100 μM had no effect on [Ca2+](i) levels or IP1 generation. In contrast, 1 mM Al3+ induced small but significant increases in both parameters. Whereas Gd3+ antagonized calcium-mediated activation of CaSR, pretreatment with Al13+ failed to block subsequent activation of rat CaSR by Ca2+, suggesting a distinct mechanism of Al3+ action. Conclusion. Al3+ is not a potent agonist for CaSR. Because Al3+ affects a variety of target tissues at micromolar concentrations, it seems unlikely that CaSR mediates these cellular actions of Al3+.

UR - http://www.scopus.com/inward/record.url?scp=0032920289&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032920289&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.1999.00432.x

DO - 10.1046/j.1523-1755.1999.00432.x

M3 - Article

VL - 55

SP - 1750

EP - 1758

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -