Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced plasma extravasation.
1 Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. 2 The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. 3 The extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. 4 Tachykinin NK(1) receptor antagonists, [D-Pro(2), D-Trp(7,9)]-SP, [D-Pro(4), D-Trp(7,9)]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK(1) receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. 5 The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP(8-37)). 6 The toxin-induced leakage was significantly inhibited by the N-type Ca(2+) channel blocker, omega-conotoxin MVIIA, and the bradykinin B(2) receptor antagonist, HOE140 (D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin), but was not affected by the selective L-type Ca(2+) channel blocker, verapamil, the P-type Ca(2+) channel blocker, omega-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na(+) channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. 7 These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK(1) receptors.
Nagahama
Masahiro
M
Department of Microbiology, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Morimitsu
Shinsuke
S
Kihara
Atsushi
A
Akita
Masahiko
M
Setsu
Koujun
K
Sakurai
Jun
J
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D004487:Edema / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; C031884:CPB protein, Clostridium perfringens; D018039:Receptors, Tachykinin