Activation of central ATP-sensitive potassium channels produces the antinociception and spinal noradrenaline turnover-enhancing effect in mice.
ICV cromakalim, a K+ channel opener, produced antinociception. This effect was completely antagonized by ICV glibenclamide, a selective adenosine triphosphate-sensitive K+ channel (KATP channel) blocker. Furthermore, direct opening of central KATP channels by ICV cromakalim increased the spinal noradrenaline (NA) turnover. On the other hand, the antinociception induced by ICV morphine (mu opioid agonist), but not ICV U-50,488H (kappa opioid agonist) was markedly potentiated by cromakalim. These findings suggest that the opening of central KATP channels may elicit the antinociceptive effect and activate the descending NAergic pathway, and central KATP channels play an important role as a modulator of the antinociception induced by mu agonists but not kappa agonists.
Narita
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Takamori
K
K
Kawashima
N
N
Funada
M
M
Kamei
J
J
Suzuki
T
T
Misawa
M
M
Nagase
H
H
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010276:Parasympatholytics / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
D000700:Analgesics; D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019806:Cromakalim; D008734:Methoxyhydroxyphenylglycol; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D000255:Adenosine Triphosphate; D005905:Glyburide; D009638:Norepinephrine