Bromoageliferin and dibromoageliferin, secondary metabolites from the marine sponge Agelas conifera, inhibit voltage-operated, but not store-operated calcium entry in PC12 cells.

Two alkaloids isolated from the marine sponge Agelas conifera were tested for interactions with cellular calcium homeostasis. Bromoageliferin and dibromoageliferin reduced voltage-dependent calcium entry in PC12 cells as measured with Fura II as calcium indicator. The half maximal concentration of both alkaloids to reduce voltage-dependent calcium entry was only slightly different: bromoageliferin showed a half maximal concentration of 6.61+/-0.33 microM, dibromoageliferin of 4.44+/-0.59 microM. Removal of calcium from extracellular solution for 10 min leads to an, at least, partial depletion of intracellular calcium stores, which induces a store-operated calcium entry after re-supplementation of calcium to the buffer. The store-operated calcium entry was unchanged by dibromoageliferin at a concentration of 30 microM, which fully blocks voltage-dependent calcium entry. The store-operated calcium entry induced by application of 5 microM thapsigargin was similarly not altered by 30 microM bromoageliferin. Both alkaloids reduce voltage-dependent calcium entry, but not store-operated calcium entry. The inhibition of voltage-operated calcium entry by bromoageliferin is shown in whole-cell patch clamp experiments.