INHIBITION OF DESERT LOCUST (SCHISTOCERCA-GREGARIA) MALPIGHIAN TUBULEFLUID 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 al l 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 destr uxin 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 secr etion was increased to 2.2 times the basal rate when Malpighian tubule s 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 intracel lular second messenger, adenosine 3',5'-cyclic monophosphate (cAMP), i n the presence of the cAMP phosphodiesterase inhibitor, 3-isobutyl-1-m ethylxanthine (IBMX). This stimulation was also abolished by destruxin A. Schistocerca Malpighian tubules continued to secrete fluid in calc ium-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 anio n channel blocker, tamido-4'-isothio-cyanatostilbene-2,2'-disulphonic acid (SITS). It is suggested that the inhibition by destruxin A of des ert locust Malpighian tubule fluid secretion involves a cellular mecha nism beyond the level of control by calcium or cAMP.