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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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The locomotory pattern of tethered wax moth larvae and the gravitational reflex of Varroa mites. a) Response of small-size wax moth larvae (WML) bitten by a honeybee, b) Response of large-size WML injected with 2.5 µL of 2-H, c) response of large-size WML injected with 1.63 mg of lidocaine d, e) modification of the gravitation reflex of Varroa exposed to 0.025 µL and 0.061 µL of 2-H (respectively), Vertical scale bar: a 3.4 mN, b 9.8 mN, c 75 μΝ, d 9.8 mN.
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pone-0047432-g003: The locomotory pattern of tethered wax moth larvae and the gravitational reflex of Varroa mites. a) Response of small-size wax moth larvae (WML) bitten by a honeybee, b) Response of large-size WML injected with 2.5 µL of 2-H, c) response of large-size WML injected with 1.63 mg of lidocaine d, e) modification of the gravitation reflex of Varroa exposed to 0.025 µL and 0.061 µL of 2-H (respectively), Vertical scale bar: a 3.4 mN, b 9.8 mN, c 75 μΝ, d 9.8 mN.

Mentions: WML exhibit a constant locomotory pattern that can easily be recorded over an extended period by gently pinning the head to a wax substrate and fixing the tail to the probe of an isometric force displacement transducer [14] (control, Fig. 3a). The locomotory pattern of the small, tethered WML (body weight 0.001–0.002 g) stopped immediately after a honeybee bite, but then gradually recovered within a few minutes (mean = 7.32 min, n = 6, SEM = ±1.51) (Fig. 3a). The locomotory pattern was not affected when we simulated a honeybee bite by applying mechanical pressure to the dorsal region of WML using a pair of fine forceps simulating the pressure caused by the bite.


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)

The locomotory pattern of tethered wax moth larvae and the gravitational reflex of Varroa mites. a) Response of small-size wax moth larvae (WML) bitten by a honeybee, b) Response of large-size WML injected with 2.5 µL of 2-H, c) response of large-size WML injected with 1.63 mg of lidocaine d, e) modification of the gravitation reflex of Varroa exposed to 0.025 µL and 0.061 µL of 2-H (respectively), Vertical scale bar: a 3.4 mN, b 9.8 mN, c 75 μΝ, d 9.8 mN.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047432-g003: The locomotory pattern of tethered wax moth larvae and the gravitational reflex of Varroa mites. a) Response of small-size wax moth larvae (WML) bitten by a honeybee, b) Response of large-size WML injected with 2.5 µL of 2-H, c) response of large-size WML injected with 1.63 mg of lidocaine d, e) modification of the gravitation reflex of Varroa exposed to 0.025 µL and 0.061 µL of 2-H (respectively), Vertical scale bar: a 3.4 mN, b 9.8 mN, c 75 μΝ, d 9.8 mN.
Mentions: WML exhibit a constant locomotory pattern that can easily be recorded over an extended period by gently pinning the head to a wax substrate and fixing the tail to the probe of an isometric force displacement transducer [14] (control, Fig. 3a). The locomotory pattern of the small, tethered WML (body weight 0.001–0.002 g) stopped immediately after a honeybee bite, but then gradually recovered within a few minutes (mean = 7.32 min, n = 6, SEM = ±1.51) (Fig. 3a). The locomotory pattern was not affected when we simulated a honeybee bite by applying mechanical pressure to the dorsal region of WML using a pair of fine forceps simulating the pressure caused by the bite.

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