Phoneutria nigriventer spider venom activates 5-HT4 receptors in rat-isolated vagus nerve.
1. The venom of Phoneutria nigriventer spider (PNV) causes intense pain and inflammation following an attack. We have investigated the involvement of capsaicin-sensitive nerve fibres by utilizing an in vitro nerve preparation. Extracellular DC potential recordings were made from the rat-isolated vagus nerve, a preparation that is rich in capsaicin-sensitive, that is, nociceptive, C-fibres. 2. PNV (1-10 microg ml(-1)), capsaicin (0.03-0.3 microM) or 5-hydroxytriptamine (5-HT) (0.3-3 microM) induced dose-dependent depolarizations of vagus nerve fibres. Depolarizing responses to capsaicin were blocked by ruthenium red (RR, 10 microM), but responses to PNV were not. Depolarizing responses to PNV or veratridine (50 microM) were inhibited by tetrodotoxin (TTX, 10 microM), but those to capsaicin were not. This suggests that capsaicin and PNV depolarize the nerve fibres by distinct mechanisms. 3. Depolarization in response to 5-HT (3 microM) was reduced by the 5-HT(3) receptor antagonists Y25130 (0.5 micro M) and tropisetron (10 nM) or, to a lesser extent, by the 5-HT(4) receptor antagonist RS39604 (1 or 10 microM). Depolarizing responses to PNV were not affected significantly by Y25130 or tropisetron, but were blocked by RS39604. 4. These data show that 5-HT(4) receptors play a significant role in the activation of nociceptive sensory nerve fibres by PNV and suggest that this is of importance in the development of the pain and inflammation associated with bites from the P. nigriventer spider.
Costa
Soraia K P
SK
Centre for Cardiovascular Biology & Medicine, New Hunt's House, King's College London, London SE1 1UL. soraia.costa@kcl.ac.uk
Brain
Susan D
SD
Antunes
Edson
E
De Nucci
Gilberto
G
Docherty
Reginald J
RJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D058828:Serotonin 5-HT4 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013111:Spider Venoms / Q000633:toxicity*; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects*
D009467:Neuromuscular Depolarizing Agents; D011955:Receptors, Drug; D058828:Serotonin 5-HT4 Receptor Agonists; D012702:Serotonin Antagonists; D013111:Spider Venoms; D012701:Serotonin; D013779:Tetrodotoxin; D002211:Capsaicin