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.
Bickmeyer
Ulf
U
Alfred-Wegener-Institut für Polar- und Meeresforschung in der Helmholtz-Gemeinschaft, Biologische Anstalt Helgoland, Kurpromenade 201, D-27498 Helgoland, Germany. ubickmeyer@awi-bremerhaven.de
D047230:Agelas / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005453:Fluorescence; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D018272:Porins / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D019284:Thapsigargin; D050994:Voltage-Dependent Anion Channels
D000470:Alkaloids; D018272:Porins; D050994:Voltage-Dependent Anion Channels; D019284:Thapsigargin; D002118:Calcium