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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 effect of 2-H, lidocaine, and other alkyl-ketones on the sciatic nerve of the rat. a) the effects of 2-H and lidocaine (Lido) on the nCAP of the rat sciatic nerve, the time-response curves for 3.41 mg/mL 2-H and lidocaine. b) the time-response curves after the preparation was washed with normal saline (recovery) and the nCAP was monitored for 24 h, c) the time-response curves for 3.41 mg/mL 2-H, 3H, 4H, d) the recovery e) 2-pentanone (2-Pe), 3-pentanone (2-Pe), 2-hexanone (2-He), 2-octanone (2-Oc) and 3-octanone (3-Oc) f) the time-response curves after the preparations were washed with normal saline (recovery) and the nCAP was monitored for 24 h.
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pone-0047432-g006: The effect of 2-H, lidocaine, and other alkyl-ketones on the sciatic nerve of the rat. a) the effects of 2-H and lidocaine (Lido) on the nCAP of the rat sciatic nerve, the time-response curves for 3.41 mg/mL 2-H and lidocaine. b) the time-response curves after the preparation was washed with normal saline (recovery) and the nCAP was monitored for 24 h, c) the time-response curves for 3.41 mg/mL 2-H, 3H, 4H, d) the recovery e) 2-pentanone (2-Pe), 3-pentanone (2-Pe), 2-hexanone (2-He), 2-octanone (2-Oc) and 3-octanone (3-Oc) f) the time-response curves after the preparations were washed with normal saline (recovery) and the nCAP was monitored for 24 h.

Mentions: Using the amplitude of the nCAP, measured from baseline to peak, we plotted the time-response curves (vitality curves) for sciatic nerves exposed to 3.41 mg/mL 2-H and lidocaine under normal stimulating conditions (Fig. 6a). We also plotted the time-response curves for three other concentrations (10.0, 2.28 and 1.41 mg/mL) and used these to estimate the time required for 100% inhibition of the nCAP (called IT0) and the time required to inhibit the amplitude of the nCAP to 50% of its control value (called IT50) (Table 2). Using the IT0 values shown in Table 2 for 2-H and lidocaine, we plotted the concentration-response curves. Thus, the IC50 was estimated to be 0.469 (SEM±0.002) for 2-H and 0.337 mg/mL for lidocaine (SEM±0.001).


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 effect of 2-H, lidocaine, and other alkyl-ketones on the sciatic nerve of the rat. a) the effects of 2-H and lidocaine (Lido) on the nCAP of the rat sciatic nerve, the time-response curves for 3.41 mg/mL 2-H and lidocaine. b) the time-response curves after the preparation was washed with normal saline (recovery) and the nCAP was monitored for 24 h, c) the time-response curves for 3.41 mg/mL 2-H, 3H, 4H, d) the recovery e) 2-pentanone (2-Pe), 3-pentanone (2-Pe), 2-hexanone (2-He), 2-octanone (2-Oc) and 3-octanone (3-Oc) f) the time-response curves after the preparations were washed with normal saline (recovery) and the nCAP was monitored for 24 h.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047432-g006: The effect of 2-H, lidocaine, and other alkyl-ketones on the sciatic nerve of the rat. a) the effects of 2-H and lidocaine (Lido) on the nCAP of the rat sciatic nerve, the time-response curves for 3.41 mg/mL 2-H and lidocaine. b) the time-response curves after the preparation was washed with normal saline (recovery) and the nCAP was monitored for 24 h, c) the time-response curves for 3.41 mg/mL 2-H, 3H, 4H, d) the recovery e) 2-pentanone (2-Pe), 3-pentanone (2-Pe), 2-hexanone (2-He), 2-octanone (2-Oc) and 3-octanone (3-Oc) f) the time-response curves after the preparations were washed with normal saline (recovery) and the nCAP was monitored for 24 h.
Mentions: Using the amplitude of the nCAP, measured from baseline to peak, we plotted the time-response curves (vitality curves) for sciatic nerves exposed to 3.41 mg/mL 2-H and lidocaine under normal stimulating conditions (Fig. 6a). We also plotted the time-response curves for three other concentrations (10.0, 2.28 and 1.41 mg/mL) and used these to estimate the time required for 100% inhibition of the nCAP (called IT0) and the time required to inhibit the amplitude of the nCAP to 50% of its control value (called IT50) (Table 2). Using the IT0 values shown in Table 2 for 2-H and lidocaine, we plotted the concentration-response curves. Thus, the IC50 was estimated to be 0.469 (SEM±0.002) for 2-H and 0.337 mg/mL for lidocaine (SEM±0.001).

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