Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats

Brazilian Journal of Medical and Biological Research

A.r.a. Rodrigues¹  M.s.a. Castro¹  J.n. Francischi¹  A.c. Perez¹  I.d.g. Duarte¹ 

[1] ,Universidade Federal de Minas Gerais Instituto de Ciências Biológicas Departamento de FarmacologiaBelo Horizonte MG ,Brasil

关键词: Peripheral antinociception;    Fentanyl;    K+ channel;    µ-Opioid receptor agonist;    Glibenclamide;   

DOI  :  10.1590/S0100-879X2005000100014

来源: SciELO

【 摘 要 】

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 µ-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 µg/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 µg/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 µg/paw) and tolbutamide (80, 160 and 240 µg/paw) dose dependently antagonized the antinociception induced by fentanyl (1.5 µg/paw). In contrast, the effect of fentanyl was unaffected by the large conductance Ca2+-activated K+ channel blocker ChTX (2 µg/paw), the small conductance Ca2+-activated K+ channel blocker apamin (10 µg/paw), or the non-specific K+ channel blocker TEA (150 µg/paw), 4-AP (50 µg/paw), and cesium (250 µg/paw). These results extend previously reported data on the peripheral analgesic effect of morphine and fentanyl, suggesting for the first time that the peripheral µ-opioid receptor-mediated antinociceptive effect of fentanyl depends on activation of ATP-sensitive, but not other, K+ channels.

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