Ionomycin acts as an ionophore to release TRH-regulated Ca2+ stores from GH4C1 cells

Am J Physiol. 1986 Dec;251(6 Pt 1):C887-91. doi: 10.1152/ajpcell.1986.251.6.C887.


In the GH4C1 strain of rat pituitary cells, ionomycin, a divalent cation ionophore, induces a rapid and transient spike in cytosolic free Ca2+ concentrations [( Ca2+]i) similar to that induced by the Ca2+-mobilizing hormone thyrotropin-releasing hormone (TRH). To test directly the hypothesis that ionomycin causes the spike in [Ca2+]i by altering cellular Ca2+ stores, we have measured ionomycin-induced changes in 45Ca2+ fluxes and have compared these to previously characterized changes induced by TRH. Ionomycin (half-maximal concentration = 30 nM) rapidly (within 1 min) induced a release into the medium of 50-60% of cell-associated 45Ca2+, paralleling the spike in [Ca2+]i. The ionomycin-induced 45Ca2+ efflux was greater than with TRH, and TRH did not induce further 45Ca2+ efflux in the presence of ionomycin. Ionomycin pretreatment blocked induction of the spike in [Ca2+]i elicited by TRH but did not alter basal or TRH-induced enhancement of inositol phosphate levels. These results provide evidence that the spike in [Ca2+]i induced by ionomycin or TRH is produced largely by release of Ca2+ into the cytosol from the same intracellular pool, followed by rapid extrusion of the released Ca2+ into the extracellular space. However, unlike TRH, ionomycin appears to release cellular Ca2+ directly, acting as an ionophore, without the generation of known second messengers.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Line
  • Ethers / pharmacology
  • Ionomycin
  • Kinetics
  • Pituitary Neoplasms
  • Rats
  • Thyrotropin-Releasing Hormone / pharmacology*


  • Ethers
  • Ionomycin
  • Thyrotropin-Releasing Hormone
  • Calcium