title: Antinociceptive action of myricitrin: involvement of the K+ and Ca2+ channels.
abstract: The present study was designed to investigate the mechanisms involved in the antinociception afforded by myricitrin in chemical models of nociception in mice. Myricitrin given by intrathecal (i.t.) or intracerebroventricular (i.c.v.) route produced dose-related antinociception when evaluated against acetic acid-induced visceral pain in mice. In addition, the intraperitoneal administration of myricitrin caused significant inhibition of biting behaviour induced by i.t. injection of glutamate, substance P, capsaicin, interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). The antinociception caused by myricitrin in the acetic acid test was fully prevented by i.t. pre-treatment with pertussis toxin, a Gi/o protein inactivator, and by i.c.v. injection of calcium chloride (CaCl(2)). In addition, the i.t. pre-treatment of mice with apamin, a blocker of small (or low)-conductance calcium-gated K(+) channels and tetraethylammonium, a blocker of voltage-gated K(+) channels significantly reversed the antinociception induced by myricitrin. The charybdotoxin, a blocker of large (or fast)-conductance calcium-gated K(+) channels and glibenclamide, a blocker of the ATP-gated K(+) channels had no effect on myricitrin-induced antinociception. Calcium uptake analysis revealed that myricitrin inhibited (45)Ca(2+) influx under a K(+)-induced depolarization condition. However, calcium movement was modified in a non-depolarizing condition only when the highest concentration of myricitrin was used. In summary, our findings indicate that myricitrin produces consistent antinociception in chemical models of nociception in mice. These results clearly demonstrate an involvement of the Gi/o protein dependent mechanism on antinociception caused by myricitrin. The opening of voltage- and small-conductance calcium-gated K(+) channels and the reduction of calcium influx led to the antinociceptive of myricitrin.
authors.affiliation: Departamento de Química, Universidade Federal de Santa Maria, 97110-000, Santa Maria, RS, Brazil.
authors.forename: Flavia Carla
authors.initials: FC
authors.lastname: Meotti
authors.forename: Roselei
authors.initials: R
authors.lastname: Fachinetto
authors.forename: Liana C
authors.initials: LC
authors.lastname: Maffi
authors.forename: Fabiana Cristina
authors.initials: FC
authors.lastname: Missau
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D019342:Acetic Acid; D000700:Analgesics; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002132:Calcium Radioisotopes; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D051379:Mice; D010146:Pain / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000700:Analgesics; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D005419:Flavonoids; D053583:Interleukin-1beta; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D018698:Glutamic Acid; C008577:myricitrin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019342:Acetic Acid; D002211:Capsaicin