| 1-Alkanols, from methanol to eicosanol, were applied to water for control of larval stage mosquitoes. By applying the alkanols as soluble solutions rather than as insoluble monolayers, and by trapping larvae under glass in assays that isolated them from the surface phenomena previously believed to be responsible for death by suffocation, the action of alkanols against mosquito larvae has been shown to be biochemical in nature, not just physical. Alkanols are known to act as general anesthetics, with increasing potency correlated to increasing chain length until a point of cutoff is reached, usually at dodecanol (C12), after which activity disappears entirely. In mosquitoes, activity leveled off after undecanol (C11) but did not disappear until after pentadecanol (C15), it was reversible, and chain length played a role not only in potency, but also in the time needed to manifest toxic effects. Sonication, a surfactant, temperature, and the introduction of double bonds were used to manipulate activity around the cutoff, suggesting it is at least partially a function of solubility. Mosquitoes are the first animal for which cutoff has been demonstrated to occur at a chain length beyond C12, offering new insights into the molecular basis of anesthetic cutoff and suggesting the possibility that alkanols might be used for selective pest control. Alkanols are stable, colorless, inexpensive, biodegradable and generally regarded as having low toxicity to humans, making them promising candidates for pest management programs.;Larvicidal activity of alkanols may involve inhibition of mitochondrial respiration. Succinate-supported respiration of mitochondria isolated from rat liver was inhibited at concentrations relevant to in vivo activity, potency peaked at undecanol, and cutoff occurred after tridecanol. Alkanols up to tridecanol also acted as uncouplers at low doses, but no direct effect on ATP synthase was apparent.;In contrast, alkanols did not inhibit respiration of freeze-thawed mitochondria, where the membranes have been broken, thereby implicating the dicarboxylate substrate carrier enzyme, rather than the electron transport chain, as the site of inhibition. This is the first study to establish the point of cutoff in intact mitochondria and the first to report inhibition of a mitochondrial substrate carrier by alkanols. |
