Role of ATP-sensitive K+ channels in antinociception induced by R-PIA, an adenosine A1 receptor agonist.
The influence of several K+ channel-acting drugs on antinociception induced by the adenosine A1 receptor agonist (-)-N6-(2-phenylisopropyl)-adenosine (R-PIA) was evaluated with a tail flick test in mice. The subcutaneous administration of R-PIA (0.5-8 mg/kg) induced a dose-dependent antinociceptive effect. The ATP-sensitive K+ (KATP) channel blocker gliquidone (2-8 micrograms/mouse, i.c.v.) produced a dose-dependent displacement to the right of the R-PIA dose-response line, whereas the KATP channel opener cromakalim (32 micrograms/mouse, i.c.v.) shifted it to the left. Several KATP channel blockers dose-dependently antagonized the antinociceptive effect of R-PIA, the order of potency being gliquidone > glipizide > glibenclamide (i.e., the same order of potency shown by these drugs in blocking KATP channels in neurons). In contrast, the K+ channel blockers 4-aminopyridine and tetraethylammonium did not antagonize the effect of R-PIA. These data suggest that antinociception produced by adenosine A1 receptor agonists is mediated by the opening of ATP-sensitive K+ channels. The present results, together with those of previous studies, further support a role for K+ channel opening in the antinociceptive effect of agonists of receptors coupled to Gi/Go proteins.
Ocaña
M
M
Department of Pharmacology, School of Medicine, University of Granada, Spain.
Baeyens
J M
JM
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology; D000698:Analgesia; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D010276:Parasympatholytics / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D011758:Pyrroles / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001578:Benzopyrans; D010276:Parasympatholytics; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D058906:Purinergic P1 Receptor Agonists; D011758:Pyrroles; D013453:Sulfonylurea Compounds; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D010660:Phenylisopropyladenosine; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine