Phoneutria nigriventer VENOM: NOVEL MECHANISMS FOR THE ACTIVATION OF SENSORY NERVES VIA 5-HT₄ RECEPTORS

Costa, S.K.P.(1)

(1)Centre for Cardiovascular Biology & Medicine and Centre for Neuroscience, King's College, London SE1 1UL, UK.

Objectives: The expression of 5-HT₄ receptor has been demonstrated in rat sensory C-fibres, thus suggesting a role in the activation of sensory neurons. Localised intense pain and neurogenico edema formation are manifestations associated with bites by the Brazilian spider Phoneutria nigriventer (Costa et al., 1997). We have used the rat isolated vagus nerve which contains sensory fibres in a grease-gap preparation to investigate Phoneutria nigriventer venom (PNV)-induced sensory nerve activation. In addition, neurogenico edema was assessed in the skin of Wistar rats (200 g) by extravasation of ¹²⁵I albumin given intravenously. Results: PNV depolarises vagus nerve in a dose-dependent manner (0.121 ± 0.02, 0.20 ± 0.02 and 0.41 ± 0.06 mV at 1, 3 and 10 mg ml^-1 respectively, n=11). Pre-treatment of the nerves with capsaicin (5 mM) desensitised the nerve to subsequent application of PNV but not KCl. The 5-HT₄ receptor antagonist RS39604 significantly inhibited PNV- (from 0.62 ± 0.13 to 0.22 ± 0.08* mV, at 1 mM, n=14) and 5-HT (from 0.67 ± 0.06 mV to 0.46 ± 0.04* mV, at 1 mM, n=13)-induced depolarisation but had no effect on capsaicin-induced response. In the rat skin in vivo, the PNV-induced plasma extravasation dependent on tachykinin NK₁ receptor activation was also significantly inhibited by RS39604.

Conclusion: Thus, our finding provides evidence that functional 5-HT₄ receptors are present at the microvascular level in rat skin and their antagonists can modulate neurogenico edema. This may contribute to growing arguments that implicates 5-HT₄ receptors in mechanisms of sensory nerve activation with respect to peripheral pain and inflammation.

REFERENCES

Costa SKP, De Nucci G, Antunes E & Brain SD. Eur J Pharmacol, 339:223-6, 1997. 

Acknowledgements: British Heart Foundation and FAPESP.

CORRESPONDENCE TO:

Soraia K P Costa, 199, New Park Road (Flat 2) Vincent Court, Streatham Hill, Londres SW2 4HP, AC, Email: soraia.costa@kcl.ac.uk