Chelates of gadolinium are used to provide enhanced contrast between healthy and diseased tissue in nuclear magnetic resonance imaging of different organs. Gadolinium is known to block many types of calcium channels such as stretch-activated and voltage-gated calcium channels. Free gadolinium is highly toxic and can cause a variety of abnormalities. Therefore, it is crucially important that gadolinium should be strongly attached to a ligand to avoid its toxic effects. Nevertheless, some chelates of gadolinium can release gadolinium ion, and they can bring about a wide variety of changes in physiology. In this study, the effects of gadolinium, gadodiamide and gadoterate meglumine on intracellular calcium signalling ([Ca2+]i) were investigated in GT1-7 cells, which are immortalized GnRH neurons. GT1-7 cells were loaded with 1 μmol Fura-2 AM and Ca2+ responses were assessed by using the fluorescent ratiometry (excitation at 340 and 380 nm, and emission at 510 nm). All data were analyzed by using an unpaired t test, with a 2-tailed P level of <0.05 defining statistical significance. Gadolinium and gadodiamide caused significant (P<0.001) reductions in KCL-induced increase in [Ca2+]i. Intracellular Ca2+ increase evoked by KCL was reduced by 33.3 ± 6.1 % (n=39) and 55.2 ± 5.1 % (n=143) in the presence of gadolinium and gadodiamide, respectively. Dotarem caused little change in [Ca2+]i, being 97.4 ± 2.4 % (n=23). These results indicate thatsome chelates of gadolinium can inhibit increase in [Ca2+]i in these neurons, which might result in side effects in reproductive functions.
We thank Dr. Pamela L. Mellon, Department of Reproductive Medicine, University of California, San Diego, for kindly providing GT1-7 cells. This study was supported by FUBAP Project No. 1972