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184 M. Kostyukovsky and E. ShaayaNerve impulseHOCHCH 2 NH 2OCH 3 CH 3NCH 3 OCH 3Acetylchol<strong>in</strong>eOHOctopam<strong>in</strong>ePost-synaptic neuronalmembraneMuscularjunctionHemolymphNerve impulseMuscular contraction,other physiological,modulatory functionsFig. 8.1. Neurotransmitters <strong>in</strong> <strong>in</strong>sect systems as possible sites of action of essentialoil toxicity.Table 8.10. Effect of essential oils <strong>in</strong> the absence and presence of the octopam<strong>in</strong>eantagonist, phentolam<strong>in</strong>e (10 –5 M), on <strong>in</strong>tracellular cyclic-AMP levels.TreatmentWithoutphentolam<strong>in</strong>eWithphentolam<strong>in</strong>eConcentration(M)Intracellular cyclic – AMP levelspmol/abdom<strong>in</strong>al segmentOctopam<strong>in</strong>e SEM76 Pulegone d-limonene0 0.210 –8 0.39 0.027 0.023 –10 –7 0.58 0.42 0.88 0.020 0.1410 –8 0.18 0.17 – –10 –7 0.05 0.17 0.2 –10 –6 0.11 0.01 – –cyclic-AMP at low physiological concentrations of 10 –8 M (Table 8.10). Moreover,addition of the octopam<strong>in</strong>e antagonist phentolam<strong>in</strong>e strongly antangonizedthe response to octopam<strong>in</strong>e, as well as to the essential oil SEM76 andpulegone, were strongly antagonized and no elevation <strong>in</strong> cyclic-AMP wasobserved (Shaaya, et al., 2001; Kostyukovsky et al., 2002b). These effects wereobserved at low dilutions of the essential oils (estimated at 10 –7 and 10 –8 M),levels that <strong>in</strong>duced the overt behavioural toxicity responses <strong>in</strong> vitro (Table8.10; Kostyukovsky et al., 2002b). It should be mentioned that d-limonene,

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