Angiotensin II receptor-mediated calcium influx in bovine adrenal glomerulosa cells

Endocrinology. 1992 Jul;131(1):408-14. doi: 10.1210/endo.131.1.1377126.


The cytoplasmic calcium ([Ca2+]i) response to angiotensin II (AII) in bovine adrenal glomerulosa cells is characterized by an initial transient peak due to intracellular Ca2+ mobilization, followed by a sustained plateau phase that is dependent on Ca2+ entry from the extracellular fluid. In Fura-2 loaded cells, the calcium channel antagonists, nifedipine (1 microM) and verapamil (20 microM), only partially reduced the cytosolic calcium profile induced by AII. The dihydropyridine agonist, Bay K 8644, caused a moderate increase in [Ca2+]i when added in concentrations of 50-100 nM, but did not enhance the AII-induced rise in [Ca2+]i. These results indicate that most of the AII-stimulated Ca2+ influx is through channels that are insensitive to dihydropyridines and verapamil. In contrast, the inorganic Ca2+ channel blocker, LaCl3 (10 microM), inhibited the AII-induced plateau phase by more than 50%. The AII-induced Ca2+ signal was not affected by treatment with pertussis toxin (100-300 ng/ml for 12 h). The prior addition of specific AII-antagonists (DuP 753, a nonpeptide antagonist, and three peptide analogs, [Sar1,Thr8]AII, [Sar1,Ala8]AII, and [Sar1,Ile8]AII) completely inhibited the AII-induced Ca2+ signal. However, addition of up to 25,000 molar excess of these antagonists at intervals from 10 sec to 5 min after AII caused progressively less attenuation of the sustained Ca2+ signal. After 5 min, addition of antagonists did not inhibit the agonist-induced Ca2+ response for up to 20 min. The progressive loss of ability of the antagonists to inhibit the sustained elevation of [Ca2+]i could reflect prolonged activation of the receptor or of a subsequent process that maintains Ca2+ influx despite receptor blockade. It is possible that sequestration and/or endocytosis of the AII-receptor complex is accompanied by continued generation of intracellular signals that contribute to the maintenance of the [Ca2+]i response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin Receptor Antagonists
  • Animals
  • Biphenyl Compounds / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / physiology
  • Cattle
  • Cells, Cultured
  • Dihydropyridines / pharmacology
  • GTP-Binding Proteins / physiology
  • Imidazoles / pharmacology
  • Lanthanum / pharmacology
  • Losartan
  • Pertussis Toxin
  • Receptors, Angiotensin / physiology*
  • Tetrazoles / pharmacology
  • Virulence Factors, Bordetella / pharmacology
  • Zona Glomerulosa / metabolism*


  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Calcium Channels
  • Dihydropyridines
  • Imidazoles
  • Receptors, Angiotensin
  • Tetrazoles
  • Virulence Factors, Bordetella
  • lanthanum chloride
  • Angiotensin II
  • Lanthanum
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • 1,4-dihydropyridine
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Losartan
  • Calcium