title: Anti-edematogenic effects of velutinol A isolated from Mandevilla velutina: evidence for a selective inhibition of kinin B1 receptor-mediated responses.
abstract: This study assesses the effects of compound velutinol A obtained from M. velutina in the rat paw edema induced by several phlogistic agents. Attempts were made to analyze how velutinol A is able to inhibit kinin B(1) receptor-mediated inflammatory responses. Velutinol A (100 nmol/paw) partially reduced (about 30%) the edema evoked by carrageenan (300 microg/paw). However, velutinol A (100 nmol/paw) failed to affect the edema induced by histamine (200 nmol/paw), substance P (30 nmol/paw), PAF (10 nmol/paw) or BK (3 nmol/paw). Interestingly, the edema caused by the selective kinin B(1) receptor agonist des-Arg(9)-BK (100 nmol/paw) in animals pre-treated with PAF or LPS was significantly inhibited by velutinol A (100 nmol/paw) (48 and 46%, respectively). A similar inhibition of des-Arg(9)-BK-induced edema after pre-treatment with PAF was obtained with the non-peptidic and selective B(1) receptor antagonist SSR 240612 (60 nmol/paw) (46%). In addition, the systemic administration of velutinol A (10 mg/kg, i.p.) or SSR 240612 (1 mg/kg, i.p.) also caused a significant reduction of des-Arg(9)-BK (100 nmol/paw)-induced edema in PAF-treated rats (51 and 43%, respectively). The results provide convincing evidence that velutinol A selectively blocks the edema responses mediated by B(1) receptor activation in vivo. This compound might represent a new non-peptidic and selective antagonist for kinin B(1) receptors.
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88049-900, Florianópolis, SC, Brazil.
authors.forename: Wilian M
authors.initials: WM
authors.lastname: Mattos
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Fernandes
authors.forename: Graziela P
authors.initials: GP
authors.lastname: Richetti
authors.forename: Rivaldo
authors.initials: R
authors.lastname: Niero
authors.forename: Rosendo A
authors.initials: RA
authors.lastname: Yunes
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists; D004149:Dioxoles / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy*; D007249:Inflammation; D007705:Kinins / Q000737:chemistry*; D008297:Male; D010936:Plant Extracts / Q000378:metabolism*; D010944:Plants / Q000378:metabolism*; D011278:Pregnanes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D065169:Bradykinin B1 Receptor Antagonists; D004149:Dioxoles; D007705:Kinins; D010936:Plant Extracts; D011278:Pregnanes; D013449:Sulfonamides; C512142:velutinol A