Presynaptic effects of the pardaxins, polypeptides isolated from the gland secretion of the flatfish Pardachirus marmoratus.

The effects of the two toxic proteins Pardaxin I and II isolated from the gland secretion of the flatfish Pardachirus marmoratus on frog neuromuscular transmission have been investigated and compared to those of the gland secretion. Pardaxin I and II showed pre- but not postsynaptic neurotoxic effects. They increased the frequency of the spontaneous release of transmitter quanta in a dose-dependent and temperature-influenced way up to more than 100 times control values. At the same time the quantal content of the evoked end-plate potentials was greatly elevated. Pardaxin I was about 5 times more effective than Pardaxin II, and both were roughly in the same range of efficacy as the original gland secretion (w/v). The glycosteroids isolated from the same gland secretion were relatively ineffective in promoting neurotransmitter release; however, at high doses they had postsynaptic effects, as shown by a diminution of the amplitude of the evoked end-plate potentials. They did not reinforce the effect of the Pardaxins. At higher doses both the Pardaxins and the gland secretion induced depolarization of postsynaptic membranes, muscle cell contractions which could not be blocked by (+)-tubocurarine or by tetrodotoxin, and eventually also physical disruption of muscle cells. No effects on nerve conductance were observed. Pore-forming activity of the Pardaxins has already been demonstrated. It is suggested that their presynaptic effects are a result of a possible affinity to the nerve terminals, of their hydrophobicity and mainly of this pore-forming activity. These toxins might be valuable tools in neuroscience research.