SURANGIN-B - INSECTICIDAL PROPERTIES AND MECHANISM UNDERLYING ITS TRANSMITTER-RELEASING ACTION IN NERVE-TERMINAL FRACTIONS-ISOLATED FROM MAMMALIAN BRAIN

Surangin B is insecticidal to Acheta domesticus by both injection (LD( 50) = 0.3 mu g) and topical application (approximate LD(50) = 2 mu g) Exposure of pure synaptosomal fractions isolated from mouse brain to l ow concentrations of surangin B results in release of the neurotransmi tters gamma-aminobutyric acid (GABA) and L-glutamate. Efflux of these neurotransmitters is accompanied by extensive depolarization of the ne rve terminal plasma membrane and a rise in intraterminal free calcium ion concentration. These events are not blocked by micromolar concentr ations of tetrodotoxin, and moderate reductions in the ability of sura ngin B to depolarize the plasma membrane and release L-glutamate are o bserved when sodium ions are excluded from the external saline. Ca2+-f ree saline produces a partial reduction in the rise in Gee [Ca2+] foll owing exposure of synaptosomes to surangin B, suggesting that an impor tant component of this compound's action is to liberate Ca2+ from an i ntracellular pool. Experiments to examine potential effects of surangi n B on energy metabolism have demonstrated that it inhibits basal oxyg en consumption by isolated nerve endings and blocks the stimulation in oxygen consumption induced by the uncoupling agent carbonyl cyanide c hlorophenylhydrazone. In addition, surangin B produces a marked and ra pid depolarization of the intraterminal mitochondrial membrane at low nanomolar concentrations. The effects we observe with surangin B on sy naptosomal mitochondrial function would be expected to (1) limit the s upply of ATP to the Na+/K+ ATPase in the plasma membrane, resulting in a failure to maintain the resting potential and (2) elicit displaceme nt of calcium ions from the mitochondrial matrix into the cytoplasm bo th of which would activate release of GABA and L-glutamate. We conclud e that depolarization of the plasma membrane, the rise in intratermina l free ionic calcium, and transmitter release observed when isolated n erve endings are exposed to surangin B are mainly consequences of its direct interference with mitochondrial function. (C) 1995 Academic Pre ss, Inc.