ISSN:
1432-1912
Keywords:
Key words: Adenosine A1 receptors – R-PIA [(–)-N6-(2-phenylisopropyl)-adenosine] – ATP-sensitive K+ channels – Sulfonylureas – Cromakalim – antinociception
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract. 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 μg/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 μg/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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00180011
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