Ixture of 125IBSA and Evans blue dye (0.1 ml of 2.5 option) was injected into the tail vein. Immediately after 5 min, betatoxin (50 ng site71) or histamine (5 mg site71) and diphenhydramine (0.1 or 0.5 mg site71) were simultaneously injected i.d. into the dorsal skin of mice. Plasma extravasation was measured 60 min after the injection of betatoxin. Values will be the means.e.imply, n=6. P50.01, compared with control,P50.001, compared with saline.Figure four Eect of tachykinin NK1 receptor antagonists on plasma extravasation induced by betatoxin in dorsal skin of mice. A mixture of 125IBSA and Evans blue dye (0.1 ml of 2.5 answer) was injected into the tail vein. Immediately after 5 min, pretreatments with many amounts of spantide and [DPro2, DTrp7, 9]SP had been performed 1 min prior to betatoxin (50 ng site71) or septide (1 nmol site71) challenge. Plasma extravasation was measured 60 min following the injection of betatoxin. Values would be the implies.e.mean, n=6. P50.05, compared with manage, P50.01, compared with handle.Next, the eect in the nonpeptide longlasting tachykinin neurokinin1 antagonist, SR140333, on the toxininduced plasma extravasation was investigated. Coinjection of SR140333 (0.1 1.0 nmol site71, or 250 500 nmole kg71 i.v. five min prior to) dosedependently inhibited the extravasation, as shown in Figure five. The plasma extravasation induced by septide (1 nmole (��)-Leucine custom synthesis site71 335.2 ml site71) was signi antly (P50.01) inhibited by coinjection of diphenhydramine (0.5 mg site71; four.81.5 ml site71) or SR140333 (1.0 nmol site71; 3.11.8 ml site71), however the histamineinduced plasma extravasation (5 mg site71; 324.5 ml site71) was not blocked by SR140333 (1.0 nmole site71; 335.2 ml site71). Septide (five mM) induced the release of about 70 of histamine from P815 cells. However, systemic remedy with 400 nmol kg71 of CGRP837 (calcitonin generelated peptide receptor antagonist) had no eect on the toxininduced extravasation (Table 1). It has been reported that the remedy of sensory nerve res with capsaicin results in the release of neuropeptides (e.g. tachykinins which include SP and calcitonin generelated peptide) and to the depletion ofBritish Journal of Pharmacology vol 138 (1)Figure 5 Eect of SR140333 therapy on plasma extravasation induced by betatoxin in dorsal skin of mice. A mixture of 125IBSA and Evans blue dye (0.1 ml of two.five solution) was injected into the tail vein. Numerous doses of SR140333 have been given as pretreatments i.d. or i.v. 5 min ahead of i.d. injection of toxin. Betatoxin (50 ng site71) and septide (1 nmole site71) were injected i.d.. Plasma extravasation was measured 60 min after the injection of betatoxin. Values will be the implies.e.imply, n=6. P50.05, compared with car, P50.01, compared with saline.neuropeptides in sensory nerves. To investigate the function of endogenous SP release from sensory nerve res on betatoxininduced plasma extravasation, the eect of a topicalM. Nagahama et alC. perfringens betatoxin and plasma extravasationadministration of capsaicin around the toxininduced extravasation was tested (Gamse et al., 1980; Alber et al., 1989; Costa et al., 1997). Topical administration of 5 capsaicin onto the dorsal back skin of mice markedly inhibited the toxininduced leakage (40 100 ng site71), as shown in Figure 6A. To exclude that the reactivity of cutaneous mast cells, histamine receptor and NK1 receptor may well be impaired after capsaicin 6-APA Purity & Documentation pretreatment, we compared the eect of compound 48/80 in a capsaicinpretreated skin website versus a manage skin sit.