Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats.
We examined the effect of several K+ channel blockers such as glibenclamide, tolbutamide, charybdotoxin (ChTX), apamin, tetraethylammonium chloride (TEA), 4-aminopyridine (4-AP), and cesium on the ability of fentanyl, a clinically used selective micro-opioid receptor agonist, to promote peripheral antinociception. Antinociception was measured by the paw pressure test in male Wistar rats weighing 180-250 g (N = 5 animals per group). Carrageenan (250 microg/paw) decreased the threshold of responsiveness to noxious pressure (delta = 188.1 +/- 5.3 g). This mechanical hyperalgesia was reduced by fentanyl (0.5, 1.5 and 3 microg/paw) in a peripherally mediated and dose-dependent fashion (17.3, 45.3 and 62.6%, respectively). The selective blockers of ATP-sensitive K+ channels glibenclamide (40, 80 and 160 microg/paw) and tolbutamide (80, 160 and 240 microg/paw) dose dependently antagonized the antinociception induced by fentanyl (1.5 microg/paw). In contrast, the effect of fentanyl was unaffected by the large conductance Ca2+-activated K+ channel blocker ChTX (2 microg/paw), the small conductance Ca2+-activated K+ channel blocker apamin (10 microg/paw), or the non-specific K+ channel blocker TEA (150 microg/paw), 4-AP (50 microg/paw), and cesium (250 microg/paw). These results extend previously reported data on the peripheral analgesic effect of morphine and fentanyl, suggesting for the first time that the peripheral micro-opioid receptor-mediated antinociceptive effect of fentanyl depends on activation of ATP-sensitive, but not other, K+ channels.
Rodrigues
A R A
AR
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Castro
M S A
MS
Francischi
J N
JN
Perez
A C
AC
Duarte
I D G
ID
D000698:Analgesia; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu
D000701:Analgesics, Opioid; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D017450:Receptors, Opioid, mu; D002351:Carrageenan; D005283:Fentanyl