Please use this identifier to cite or link to this item: http://ktisis.cut.ac.cy/handle/10488/3648
Title: The Bite of the Honeybee: 2-Heptanone Secreted from Honeybee Mandibles during a Bite Acts as a Local Anaesthetic in Insects and Mammals
Authors: Papachristoforou, Alexandros 
Kagiava, Alexia 
Papaefthimiou, Chrisovalantis 
Termentzi, Aikaterini 
Fokialakis, Nikolas 
Skaltsounis, Alexios-Leandros 
Watkins, Max 
Arnold, Gerard 
Theophilidis, George 
Keywords: Rat sciatic-nerve
Apis-mellifera-carnica
Varroa-destructor
Sodium-channels
In-vitro
Neurotoxicity
Pheromones
Issue Date: 2012
Publisher: Public Library Science
Source: PLOS ONE Volume: 7 Issue:10 Pages:-
Abstract: Honeybees secrete 2-heptanone (2-H) from their mandibular glands when they bite. Researchers have identified several possible functions: 2-H could act as an alarm pheromone to recruit guards and soldiers, it could act as a chemical marker, or it could have some other function. The actual role of 2-H in honeybee behaviour remains unresolved. In this study, we show that 2-H acts as an anaesthetic in small arthropods, such as wax moth larva (WML) and Varroa mites, which are paralysed after a honeybee bite. We demonstrated that honeybee mandibles can penetrate the cuticle of WML, introducing less than one nanolitre of 2-H into the WML open circulatory system and causing instantaneous anaesthetization that lasts for a few minutes. The first indication that 2-H acts as a local anaesthetic was that its effect on larval response, inhibition and recovery is very similar to that of lidocaine. We compared the inhibitory effects of 2-H and lidocaine on voltage-gated sodium channels. Although both compounds blocked the hNav1.6 and hNav1.2 channels, lidocaine was slightly more effective, 2.82 times, on hNav.6. In contrast, when the two compounds were tested using an ex vivo preparation-the isolated rat sciatic nerve-the function of the two compounds was so similar that we were able to definitively classify 2-H as a local anaesthetic. Using the same method, we showed that 2-H has the fastest inhibitory effect of all alkyl-ketones tested, including the isomers 3- and 4-heptanone. This suggests that natural selection may have favoured 2-H over other, similar compounds because of the associated fitness advantages it confers. Our results reveal a previously unknown role of 2-H in honeybee defensive behaviour and due to its minor neurotoxicity show potential for developing a new local anaesthetic from a natural product, which could be used in human and veterinary medicine.
Description: The research was directed and funded by Vita (Europe) Limited, UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors have read the journal's policy and have the following conflicts: the research was funded through Vita (Europe) Limited, a small UK company specialising only in honeybee health. MW works for this company. The original studies examined honeybee behaviour and they discovered the anaesthetisation properties of 2-H in the mammalian peripheral nervous systems as an extension to the honeybee biology work. Vita has now filed a patent on the potential use of 2-heptanone as a local anaesthetic (International Patent Application number: PCT/GB2012/050157). This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist.We thank the Cypriot Union of Beekeepers for providing the specimens for the trials. We thank Evagelos Gikas for analytical advice, Dimitris Fotaroudis for the statistical support, ChanTest Corporation (Cleveland OH, US) for the support on patch-clamp experiments and Sharilynn Wardrop for reviewing the paper. We thank Anais Carpentier for the support during SEM photography, which benefited from the facilities and expertise of the Imagif Cell Biology Unit of the Gif campus (www.imagif.cnrs.fr) which is supported by the Conseil General de l' Essonne.
URI: http://ktisis.cut.ac.cy/jspui/handle/10488/3648
http://hdl.handle.net/10488/3648
Other Identifiers: 1932-6203
DOI: 10.1371/journal.pone.0047432
Rights: Public Library Science
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