Calcium oscillations in parotid acinar cells induced by microsomal Ca(2+)-ATPase inhibition

Am J Physiol. 1992 Mar;262(3 Pt 1):C656-63. doi: 10.1152/ajpcell.1992.262.3.C656.


Previous studies have demonstrated in single rat parotid acinar cells that the microsomal Ca(2+)-ATPase inhibitor thapsigargin mobilizes Ca2+ specifically from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store, activates plasma membrane Ca2+ permeability, and induces intracellular Ca2+ concentration ([Ca2+]i) oscillations that are quite similar to those activated by carbachol. Nevertheless, the IP3-sensitive Ca2+ store remains continuously depleted during thapsigargin-induced oscillations, indicating that this pool is not involved in the oscillation mechanism. To determine the specificity of thapsigargin's effects, in the present study we have examined the effects on [Ca2+]i in single rat parotid acinar cells of two other microsomal Ca(2+)-ATPase inhibitors, cyclopiazonic acid (CPA) and 2,5-di-tert-butyl-1,4-benzohydroquinone (BHQ), and compared them with the effects of thapsigargin in the same cells. Our results demonstrate that thapsigargin, CPA, and BHQ all similarly deplete the IP3-sensitive Ca2+ store specifically, activate plasma membrane Ca2+ influx, and induce [Ca2+]i oscillations, strongly suggesting that these agents have a specific inhibitory action on microsomal Ca(2+)-ATPase activity. BHQ, in addition, inhibits plasma membrane Ca2+ influx. The data lend strong support to a model in which the state of Ca2+ filling of the IP3-sensitive store regulates plasma membrane Ca2+ influx. These results suggest either that a Ca2+ pump is involved which is insensitive to structurally dissimilar inhibitors or that a Ca2+ pump is not involved in refilling of the Ca2+ pool involved in [Ca2+]i oscillations in these cells.

Publication types

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

MeSH terms

  • Animals
  • Benzoquinones / pharmacology
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors*
  • Calcium-Transporting ATPases / metabolism
  • Carbachol / pharmacology
  • Cell Membrane Permeability / drug effects
  • Fura-2
  • In Vitro Techniques
  • Indoles / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Kinetics
  • Male
  • Microsomes / enzymology*
  • Parotid Gland / cytology
  • Parotid Gland / drug effects
  • Parotid Gland / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Terpenes / pharmacology*
  • Thapsigargin


  • Benzoquinones
  • Indoles
  • Terpenes
  • 2,5-di-tert-butylbenzoquinone
  • Thapsigargin
  • Inositol 1,4,5-Trisphosphate
  • Carbachol
  • Calcium-Transporting ATPases
  • Calcium
  • Fura-2
  • cyclopiazonic acid