Cromakalim differentially enhances antinociception induced by agonists of alpha(2)adrenoceptors, gamma-aminobutyric acid(B), mu and kappa opioid receptors.
The influence of the ATP-sensitive K+(KATP) channel opener cromakalim on the antinociception induced by agonists of several receptors coupled to pertussis toxin-sensitive G proteins, clonidine (alpha2 adrenoceptor), 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 clonidine (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 effect. Cromakalim (8-64 microgram/mouse intracerebroventricularly [i.c.v.]) did not change tail-flick latency in control animals but produced a dose-dependent enhancement of the antinociception induced by clonidine and morphine, and shifted their dose-response curves to the left. These effects of cromakalim were antagonized dose dependently by the K(ATP) channel blocker gliquidone (0.1-8 microgram/mouse i.c.v.). On the other hand, cromakalim (16-64 microgram/mouse i.c.v.) did not significantly enhance the 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 induced by gamma-aminobutyric acid(B) and kappa opioid receptors.
Ocaña
M
M
Department of Pharmacology, School of Medicine, University of Granada, Spain.
Barrios
M
M
Baeyens
J M
JM
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D011758:Pyrroles / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D011758:Pyrroles; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014665:Vasodilator Agents; D019806:Cromakalim; D009020:Morphine; D001418:Baclofen