Cker TTXresistant Na channel 1-Hydroxy-2-naphthoic acid custom synthesis blocker Administration 3.2 mg kg71, i.v. one hundred pmole site71, i.d. 60 mg kg71, i.v. 400 nmole kg71, i.v. 3 nmole site71, i.d. 1 mg site71, i.d. 120 mmole kg71, i.v. 1 nmole site71, i.d. 25 mg kg71, i.v. Plasma ACE Inhibitors Related Products extravasation (ml site71) 39.66.9 6.82.3 31.45.1 32.84.3 40.27.three 16.35.five 39.46.8 37.46.5 31.45.1 38.47.Betatoxin (50 ng site71) was injected i.d. into mouse dorsal skin in the presence of different drugs injected i.d. or i.v. or as shown within the Table. Values will be the implies.e.mean, n=8. P50.01, compared with vehicle, P50.05, compared with vehicle. British Journal of Pharmacology vol 138 (1)M. Nagahama et alC. perfringens betatoxin and plasma extravasation(1996), carbamazepine known as a TTXresistant Na channel blocker (Arbuckle Docherty, 1995; Akopian et al., 1996) and lignocaine referred to as a sensory nerve conduction blocker (Escott et al., 1995), didn’t signi antly inhibit the toxininduced leakage, as shown in Table 1.DiscussionC. perfringens betatoxin injected in animal skin is identified to cause a characteristic purplish dermonecrosis. Within this study, histopathological evaluation revealed that the toxin induced oedema formation and necrosis when injected inside the mouse dorsal skin as shown in Figure 2. The data presented here are the st to become published displaying that the toxininduced plasma extravasation includes a tachykinin NK1 receptormediated mechanism. Right after injection of betatoxin into mouse, the mainly clinical manifestation is nervous signs which includes tetany and opisthotonus. We reported that the toxin acts on the autonomic nervous system and produces arterial constriction (Sakurai et al., 1981, 1984). On the basis of these results, we proposed that the toxininduced oedema is dependent on action from the toxin on peripheral nerve systems in skin. When betatoxin was injected i.d. in mouse skin, plasma extravasation was initially formed inside 120 min and dermonecrosis was observed more than 6 h, suggesting that the toxininduced plasma extravasation outcomes in reduction or block in help of nutrients and oxygen in the skin tissue and consequently, the toxin is destroyed to create to dermonecrosis. Nevertheless, the connection between oedema formation and dermonecrosis just isn’t clear. Coinjection of the histamine H1 receptor antagonist, diphenhydramine (0.1 mg site71), markedly inhibited the toxininduced plasma extravasation, suggesting that the activity from the toxin is closely related towards the release of histamine from skin mast cells. Nevertheless, the toxin didn’t induce the release of histamine from rat mast cells (Sakurai Fujii, 1987) and P815 cells. It consequently is most likely that the toxin indirectly acts on mast cells and induces the release of histamine in the cells. EmondsAlt et al. (1993) reported that SR140333 acts as a potent tachykinin NK1 receptor antagonist in vitro and in vivo in many species. Additionally, Palframan et al. (1996) described the selectivity of SR140333 at the NK1 receptor, when injected intradermally in rat skin. Additionally, it has been reported that capsaicin stimulates sensory nerve res to outcome within the release of neuropeptides for instance tachykinins, showing that capsaicin pretreatment abolished neuropeptides in sensory nerve res (Gamse et al., 1980; Alber et al., 1989; Costa et al., 1997). To investigate the toxininduced extravasation, we tested dierent classes of drugs that act on sensory nerves, presynaptic receptors or postsynaptic receptors. The results in the use of those blockers.