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The bite of the honeybee: 2-heptanone secreted from honeybee mandibles during a bite acts as a local anaesthetic in insects and mammals.

Papachristoforou A, Kagiava A, Papaefthimiou C, Termentzi A, Fokialakis N, Skaltsounis AL, Watkins M, Arnold G, Theophilidis G - PLoS ONE (2012)

Bottom Line: We compared the inhibitory effects of 2-H and lidocaine on voltage-gated sodium channels.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece. papachri@legs.cnrs-gif.fr

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.

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Related in: MedlinePlus

Number of honeybees exiting beehives following 2-H applications. No treatment (control) and doses of 0.001, 10 and 1000 µL of 2-H were applied at the colony entrance. Honeybees were recorded using Electronic BeeSCAN counters.
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pone-0047432-g001: Number of honeybees exiting beehives following 2-H applications. No treatment (control) and doses of 0.001, 10 and 1000 µL of 2-H were applied at the colony entrance. Honeybees were recorded using Electronic BeeSCAN counters.

Mentions: We first tested the dominant hypothesis that honeybees secrete 2-H as an alarm pheromone that recruits other honeybees in the face of a potential threat. We monitored honeybee response to different doses of 2-H applied at colony entrances. In control colonies, which were not exposed to 2-H, an average of 46.42 bees left the colony per minute (n = 5, SEM = 0.43). There was no statistical difference, 10 minutes after application, between the mean number of bees recruited in control colonies and those recruited in colonies exposed to 0.1 µL 2-H (mean = 47.18, n = 5, SEM = 0.36, p = 1.000). In contrast, higher doses of 2-H acted as a repellent. Compared to controls, significantly fewer honeybees exited the hive per minute in colonies exposed to 10 µL 2-H (mean = 42.54, n = 5, SEM = 0.11, p = 0.003) and to 1000 µL 2-H (mean = 40.88 honeybees, n = 5, SEM = 0.42, p = 0.002) (Fig. 1). The above results clearly show that the application of 2-H did not recruit honeybees from the nest cavity and triggered no defensive responses (no attack on the filter papers containing 2-H).


The bite of the honeybee: 2-heptanone secreted from honeybee mandibles during a bite acts as a local anaesthetic in insects and mammals.

Papachristoforou A, Kagiava A, Papaefthimiou C, Termentzi A, Fokialakis N, Skaltsounis AL, Watkins M, Arnold G, Theophilidis G - PLoS ONE (2012)

Number of honeybees exiting beehives following 2-H applications. No treatment (control) and doses of 0.001, 10 and 1000 µL of 2-H were applied at the colony entrance. Honeybees were recorded using Electronic BeeSCAN counters.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3472974&req=5

pone-0047432-g001: Number of honeybees exiting beehives following 2-H applications. No treatment (control) and doses of 0.001, 10 and 1000 µL of 2-H were applied at the colony entrance. Honeybees were recorded using Electronic BeeSCAN counters.
Mentions: We first tested the dominant hypothesis that honeybees secrete 2-H as an alarm pheromone that recruits other honeybees in the face of a potential threat. We monitored honeybee response to different doses of 2-H applied at colony entrances. In control colonies, which were not exposed to 2-H, an average of 46.42 bees left the colony per minute (n = 5, SEM = 0.43). There was no statistical difference, 10 minutes after application, between the mean number of bees recruited in control colonies and those recruited in colonies exposed to 0.1 µL 2-H (mean = 47.18, n = 5, SEM = 0.36, p = 1.000). In contrast, higher doses of 2-H acted as a repellent. Compared to controls, significantly fewer honeybees exited the hive per minute in colonies exposed to 10 µL 2-H (mean = 42.54, n = 5, SEM = 0.11, p = 0.003) and to 1000 µL 2-H (mean = 40.88 honeybees, n = 5, SEM = 0.42, p = 0.002) (Fig. 1). The above results clearly show that the application of 2-H did not recruit honeybees from the nest cavity and triggered no defensive responses (no attack on the filter papers containing 2-H).

Bottom Line: We compared the inhibitory effects of 2-H and lidocaine on voltage-gated sodium channels.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece. papachri@legs.cnrs-gif.fr

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.

Show MeSH
Related in: MedlinePlus