CROMAKALIM DIFFERENTIALLY ENHANCES ANTINOCICEPTION INDUCED BY AGONISTS OF ALPHA(2) ADRENOCEPTORS, GAMMA-AMINOBUTYRIC ACID(B), MU-OPIOID ANDKAPPA-OPIOID RECEPTORS

The influence of the ATP-sensitive K+ (K-ATP) channel opener cromakali m on the antinociception induced by agonists of several receptors coup led to pertussis toxin-sensitive G proteins, clonidine (alpha(2) adren oceptor), baclofen (gamma-aminobutyric acid(B) receptor), morphine (mu opioid receptor) and U50,488H (kappa opioid receptor), was evaluated with a tail-flick test in mice. The subcutaneous administration of clo nidine (0.12-2 mg/kg), morphine (0.5-16 mg/kg), baclofen (2-16 mg/kg) and U50,488H (2-16 mg/kg) induced a dose-dependent antinociceptive eff ect. Cromakalim (8-64 mu g/mouse intracerebroventricularly [i.c.v.]) d id not change tail-flick latency in control animals but produced a dos e-dependent enhancement of the antinociception induced by clonidine an d morphine, and shifted their dose-response curves to the left. These effects of cromakalim were antagonized dose dependently by the K-ATP c hannel blocker gliquidone (0.1-8 mu g/mouse i.c.v.). On the other hand , cromakalim (16-64 mu g/mouse i.c.v.) did not significantly enhance t he antinociception induced by baclofen and U50,488H and did not shift their dose-response curves. These results suggest that opening of the K-ATP channels plays an important role in the antinociception mediated by alpha(2) adrenoceptors and mu opioid receptors, but not in that in duced by gamma-aminobutyric acid(B) and kappa opioid receptors.