Neurotoxic effects of caulerpenyne.

1. In this paper the authors tested the effect of caulerpenyne (CYN), a sesquiterpene synthesized by the green alga Caulerpa taxifolia onto the central nervous system of the leech Hirudo medicinalis. Investigations have been performed with three different approaches: neuroethological, electrophysiological and neurochemical techniques. 2. CYN application mimics the effect of a nociceptive stimulation (brushing), eliciting a clear-cut potentiation of the animal swim response to the test stimulus (non associative learning process such as sensitization). This effect is similar to that one induced by the endogenous neurotransmitter serotonin (5HT). 3. CYN strongly reduces the after-hyperpolarization (AHP) recorded from T sensory neurons. This effect overlaps that one produced by 5HT, but it is not affected by the serotonergic antagonist methysergide. 4. The decrease of AHP amplitude due to CYN application is observed also in presence of apamin, a blocking agent of Ca++-dependent K+ channels, suggesting that CYN is acting through the inhibition of the Na+/K+ electrogenic pump. 5. The depression of the AHP driven by CYN is not prevented by application of MDL 12330A, an adenylate cyclase inhibitor. On the other hand MDL 12330A counteracts the reduction of AHP due to 5HT application. 6. Incubation of the leech central nervous system with CYN induces the phosphorylation of proteins of 29, 50, 66 and 100 kDa. This pattern of phosphorylation is similar to that one elicited by 5HT treatment. 7. The data demonstrate that CYN exerts remarkable effects on leech neurons by acting onto specific molecular targets such as the Na+/K+ ATPase. This effect may influence important neural integrative functions and may explain the sensitizing action produced by the toxin on swim induction. Finally, caulerpenyne does not act through the pathways involved in the 5HT action, and its effect is not mediated by the second messenger cyclic AMP. The mechanism of action of CYN are still under investigations.