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

• Published in: The American journal of physiology Vol. 251; no. 6 Pt 1; pp. C887 - C891
• Main Authors: Albert, P R, Tashjian, Jr, A H
• Format: Journal Article
• Language: English
• Published: United States 01-12-1986
• Subjects: Animals; Calcium - metabolism; Cell Line; Ethers - pharmacology; Ionomycin; Kinetics; Pituitary Neoplasms; Rats; Thyrotropin-Releasing Hormone - pharmacology
• ISSN: 0002-9513
• 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.