title: Possible participation of nitric oxide/cyclic guanosine monophosphate/protein kinase C/ATP-sensitive K(+) channels pathway in the systemic antinociception of flavokawin B.
abstract: The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
authors.forename: Azam Shah
authors.initials: AS
authors.lastname: Mohamad
authors.forename: Muhammad Nadeem
authors.initials: MN
authors.lastname: Akhtar
authors.forename: Shaik Ibrahim
authors.initials: SI
authors.lastname: Khalivulla
authors.forename: Enoch Kumar
authors.initials: EK
authors.lastname: Perimal
authors.forename: Mohamed Hanief
authors.initials: MH
authors.lastname: Khalid
authors.forename: Hui Ming
authors.initials: HM
authors.lastname: Ong
authors.forename: Seema
authors.initials: S
authors.lastname: Zareen
authors.forename: Ahmad
authors.initials: A
authors.lastname: Akira
authors.forename: Daud Ahmad
authors.initials: DA
authors.lastname: Israf
authors.forename: Nordin
authors.initials: N
authors.lastname: Lajis
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007004:Hypoglycemic Agents; D015221:Potassium Channels; C452039:flavokawain B; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D006152:Cyclic GMP; D005905:Glyburide; D008751:Methylene Blue