Involvement of potassium channels in spinal antinociceptions induced by fentanyl, clonidine and bethanechol in rats.
In the central nervous systems, intracellular and extracellular movement of potassium ions plays an important role in regulating neuronal excitability and the release of neurotransmitters. The purpose of our study was to determine whether nicorandil (adenosine triphosphate-sensitive K+ channel opener) exerts antinociceptive effects by itself or in combination with fentanyl, clonidine and bethanechol and whether glibenclamide (adenosine triphosphate-sensitive K+ channel blocker) and charybdotoxin (Ca2+-activated K+ channel blocker) may antagonize the antinociceptive action of fentanyl, clonidine and bethanechol. Antinociceptive effects were assessed using the tail-flick test in rats. Nicorandil (100 microg) and antinociceptively ineffective doses of fentanyl (1 microg), clonidine (2.5 microg) or bethanechol (10,ug) were coadministered intrathecally (i.t.). Glibenclamide (100 microg) or charybdotoxin (2.5 ng) were administered i.t. at 5 min before each effective dose of fentanyl (2.5 microg), clonidine (10 microg) or bethanechol (40 microg). The present findings demonstrated that i.t. administration of nicorandil alone exerted no influence on the tail-flick latency. However, concomitant administrations of antinociceptively inactive doses of fentanyl, clonidine or bethanechol with nicorandil elicited significant suppression of the thermonociceptive response. Also, each antinociception induced by fentanyl, clonidine or bethanechol was partially antagonized by both glibenclamide and charybdotoxin. These findings showed that activation of the K+ channel might enhance the antinociceptive effects of fentanyl, clonidine and bethanechol.
Yamazumi
I
I
Department of Anesthesiology, Kinki University School of Medicine, Osakasayama, Osaka, Japan. isy@ma.neweb.ne.jp
Okuda
T
T
Koga
Y
Y
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D020108:Nicorandil / Q000627:therapeutic use; D010147:Pain Measurement / Q000187:drug effects; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018723:Bethanechol; D018999:Charybdotoxin; D020108:Nicorandil; D000251:Adenosine Triphosphatases; D003000:Clonidine; D005905:Glyburide; D005283:Fentanyl