RT Journal Article SR Electronic T1 Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 13 OP 19 DO 10.1124/jpet.115.226787 VO 356 IS 1 A1 Rocha-e-Silva, Thomaz A. A. A1 Linardi, Alessandra A1 Antunes, Edson A1 Hyslop, Stephen YR 2016 UL http://jpet.aspetjournals.org/content/356/1/13.abstract AB Bites by tarantulas (Theraphosidae, Mygalomorphae) in humans can result in mild clinical manifestations such as local pain, erythema, and edema. Vitalius dubius is a medium-sized, nonaggressive theraphosid found in southeastern Brazil. In this work, we investigated the mediators involved in the plasma extravasation caused by V. dubius venom in rats. The venom caused dose-dependent (0.1–100 μg/site) edema in rat dorsal skin. This edema was significantly inhibited by ((S)1-{2-[3(3-4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)piperidine-3-yl]ethyl}-4-phenyl-1-azoniabicyclo[2.2.2]octone, chloride) (SR140333, a neurokinin NK1 receptor antagonist), indomethacin [a nonselective cyclooxygenase (COX) inhibitor], cyproheptadine (a serotonin 5-hydroxytryptamine1/2 and histamine H1 receptor antagonist), and Nω-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor). In contrast, mepyramine (a histamine H1 receptor antagonist), D-Arg-[Hyp3,Thi5,D-Tic7,Oic8-]-BK (JE 049, a bradykinin B2 receptor antagonist), and ((S)-N-methyl-N-[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-di-chlorophenyl)butyl]benzamide) (SR48968, a neurokinin NK2 receptor antagonist) had no effect on the venom-induced increase in vascular permeability. In rat hind paws, the venom-induced edema was attenuated by ketoprofen (a nonselective COX inhibitor) administered 15 minutes postvenom. Preincubation of venom with commercial antiarachnid antivenom attenuated the venom-induced edema. These results suggest that the enhanced vascular permeability evoked by V. dubius venom involves serotonin, COX products, neurokinin NK1 receptors, and nitric oxide formation. The attenuation of hind paw edema by ketoprofen suggests that COX inhibitors could be useful in treating the local inflammatory response to bites by these spiders.