Mechanisms involved in the antinociception caused by compound MV8612 isolated from Mandevilla velutina in mice.
The pregnane compound MV8612 isolated from the rhizome of the plant Mandevilla velutina administered by intraperitoneal (i.p.), intrathecal (i.t.) or by intracerebroventricular (i.c.v.) routes caused graded and complete inhibition of the thermal hyperalgesia caused by i.t. injection of bradykinin (BK) in mice with mean ID(50) values of 7.8 micromol/kg, 33.6 and 4.6 nmol/site, respectively. Compound MV8612 (i.p.) also inhibited both the neurogenic and inflammatory pain responses to formalin with mean ID(50) values of 5.6 and 10.6 micromol/kg, respectively. Given i.t., MV8612 produced significant inhibition of both phases of the formalin-induced licking (inhibition of 34+/-5 and 36+/-4%, respectively). Given by i.c.v. route MV8612 inhibited both phases of formalin-induced pain (32+/-6 and 63+/-5%) with mean ID(50) of 8.4 nmol/site against the late phase. MV8612, given by i.p., i.c.v. or i.t. routes, also inhibited capsaicin-induced pain (51+/-4, 25+/-8 and 39+/-6%, respectively). The i.t. injection of potassium (K(+)) channel blockers, apamin and charybdotoxin given 15 min before, markedly prevented the antinociception of MV8612 against both phases of formalin-induced nociception. In contrast, tetraethylammonium (TEA) or glibenclamide had no effect. The i.c.v. treatment with pertussis toxin resulted in a significant inhibition of both MV8612- and morphine-induced antinociception against both phases of formalin-induced pain. Taken together these results confirm and also extend our previous data by demonstrating that the greater part of the antinociception caused by MV8612 seems to be associated with its ability to interfere with BK action. Finally, both the low and high conductance calcium (Ca(2+))-activated K(+) channels and the activation of G(i/o) pertussis sensitive G-proteins take part in the mechanism by which compound MV8612 produces antinociception.
Santos
Adair R S
AR
Department of Pharmacology, Centre of Biological Sciences, Federal University of Santa Catarina, Rua Ferreira Lima, 82, 88015-420, Florianópolis, SC, Brazil.
Trentin
Ana Paula
AP
Ferreira
Juliano
J
Yunes
Rosendo A
RA
Calixto
João B
JB
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001920:Bradykinin; D002211:Capsaicin; D018999:Charybdotoxin / Q000494:pharmacology; D005557:Formaldehyde; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced; D037342:Pertussis Toxin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D013256:Steroids / Q000008:administration & dosage / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology
D000700:Analgesics; D006027:Glycosides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013256:Steroids; D018999:Charybdotoxin; C085132:MV 8612; D005557:Formaldehyde; D001030:Apamin; D019789:Tetraethylammonium; D009020:Morphine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002211:Capsaicin; D001920:Bradykinin; D005905:Glyburide