Modulation of cytosolic calcium levels of human lymphocytes by yessotoxin,a novel marine phycotoxin

Yessotoxin (YTX) is a polyether toxin of marine origin that has been classi fied among the diarrheic shellfish poisoning (DSP) toxins group due to its lipophilic nature. However, unlike other DSP toxins, YTX does not produce d iarrhea and its mechanisms of action are unknown. We studied the effect of YTX on the cytosolic calcium levels of freshly isolated human lymphocytes b y means of fluorescence imaging microscopy. We showed that YTX produced a c alcium influx through nifedipine and SKF 96365 (1-[beta-[3-(4-methoxyphenyl )propoxyl]-4-methoxyphenyl]-1H-imidazole hydrochloride)-sensitive channels. This Ca2+ entry was not affected by the DSP toxin okadaic acid, which inhi bits protein phosphatases. In addition, YTX also produced an inhibition of capacitative calcium entry activated by thapsigargin or by preincubation in a Ca2+-free medium. This capacitative calcium entry was not sensitive to n ifedipine. Furthermore, the inhibitory effect of YTX was dependent on the t ime of addition of the toxin. We suggest that YTX may interact with calcium channels in a way similar to that described for other polyether marine com pounds such as brevetoxins and maitotoxin, although an involvement of other second messengers is also likely. (C) 2001 Elsevier Science Inc. All right s reserved.