INHIBITION OF DESERT LOCUST (SCHISTOCERCA-GREGARIA) MALPIGHIAN TUBULE FLUID SECRETION BY DESTRUXINS, CYCLIC PEPTIDE TOXINS FROM THE INSECT PATHOGENIC FUNGUS METARHIZIUM-ANISOPLIAE

Destruxins are cyclic peptide lactone toxins isolated from the insect pathogenic fungus Metarhizium anisopliae. Destruxins A, A2, B and E all inhibit fluid secretion in vitro by Malpighian tubules of the desert locust Schistocerca gregaria. Inhibition is dose-dependent; the IC50 for destruxin A is 23 muM. Destruxins A2, B and E are similar to destruxin A in their effectiveness on fluid secretion at a concentration of 16 muM. Following a brief exposure to destruxin A in vitro, the rate of fluid secretion recovers significantly but incompletely. Fluid secretion was increased to 2.2 times the basal rate when Malpighian tubules were exposed to synthetic Locusta migratoria diuretic peptide. This stimulation of fluid secretion was completely inhibited by destruxin A. Fluid secretion by Malpighian tubules was stimulated by the intracellular second messenger, adenosine 3',5'-cyclic monophosphate (cAMP), in the presence of the cAMP phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). This stimulation was also abolished by destruxin A. Schistocerca Malpighian tubules continued to secrete fluid in calcium-free conditions (zero calcium saline with added EGTA). Destruxin A inhibited fluid secretion equally well in the absence or presence of external calcium. The calcium channel blocker cadmium chloride did not prevent inhibition of fluid secretion by destruxin A nor did the anion channel blocker, 4-acetamido-4'-isothio-cyanatostilbene-2,2'-disulphonic acid (SITS). It is suggested that the inhibition by destruxin A of desert locust Malpighian tubule fluid secretion involves a cellular mechanism beyond the level of control by calcium or cAMP.