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

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Rodrigues AR, Castro MS, Francischi JN, Perez AC, Duarte ID

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

Braz J Med Biol Res. 2005 Jan;38(1):91-7. Epub 2005 Jan 18.

PubMed ID

15665994 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
3-Methylthiofentanyl	Delta-type opioid receptor	Protein	Humans	Yes	Agonist	Details
Fentanyl	Delta-type opioid receptor	Protein	Humans	Yes	Agonist	Details
Remifentanil	Delta-type opioid receptor	Protein	Humans	Unknown	Agonist	Details