ENANTIOSPECIFIC SYNTHESIS OF BIOACTIVE HYDROXYEICOSATETRAENOIC ACIDS (HETES) IN HYDRA-MAGNIPAPILLATA

Recent reports have shown the occurrence of regiospecific and enantios elective lipoxygenase-mediated metabolism of arachidonic acid (AA) in cytosolic extracts of marine and freshwater hydroids. Here we report t hat cytosolic extracts of Hydra magnipapillata are unique among hydroz oans for their capability of converting AA into two major metabolites which showed chromatographic, mass spectrometric and nuclear magnetic resonance properties identical to those of 11-R- and 12-S-hydroxy-eico satetraenoic acid (11-R-HETE and 12-S-HETE). The production of neither compound was affected by co-incubation of H. magnipapillata extracts with the cytochrome P-450 inhibitor proadifen. The 5- and 12-lipoxygen ase inhibitor nordihydroguaiaretic acid (NDGA), while inhibiting 12-S- HETE formation at high concentrations, did not influence 11-R-HETE pro duction, thus suggesting the co-localisation, unprecedented in hydroid s, of two separate enantioselective lipoxygenase-like activities. The possible role of the two metabolites in the control of hydroid body pa ttern was investigated. At low micromolar concentrations, both enantio mers of 11-HETE inhibited diacylglycerol-induced ectopic head formatio n (EHF), while 12-S-HETE, and its likely precursor 12-S-hydroperoxy-ei cosatetraenoic acid (12-S-HPETE), enhanced bud formation, thus providi ng the first example of endogenous metabolites controlling, respective ly, hydroid 'head activation potential' and asexual reproduction.