title: Differential effects of K+ channel blockers on antinociception induced by alpha 2-adrenoceptor, GABAB and kappa-opioid receptor agonists.
abstract: 1. The effects of several K+ channel blockers (sulphonylureas, 4-aminopyridine and tetraethylammonium) on the antinociception induced by clonidine, baclofen and U50,488H were evaluated by use of a tail flick test in mice. 2. Clonidine (0.125-2 mg kg-1, s.c.) induced a dose-dependent antinociceptive effect. The ATP-dependent K+ (KATP) channel blocker gliquidone (4-8 micrograms/mouse, i.c.v.) produced a dose-dependent displacement to the right of the clonidine dose-response line, but neither 4-aminopyridine (4-AP) (25-250 ng/mouse, i.c.v.) nor tetraethylammonium (TEA) (10-20 micrograms/mouse, i.c.v.) significantly modified clonidine-induced antinociception. 3. The order of potency of sulphonylureas in antagonizing clonidine-induced antinociception was gliquidone > glipizide > glibenclamide > tolbutamide, which is the same order of potency as these drugs block KATP channels in neurones of the CNS. 4. Baclofen (2-16 mg kg-1, s.c.) also induced a dose-dependent antinociceptive effect. Both 4-AP (2.5-25 ng/mouse, i.c.v.) and TEA (10-20 micrograms/mouse, i.c.v.) dose-dependently antagonized baclofen antinociception, producing a displacement to the right of the baclofen dose-response line. However, gliquidone (8-16 micrograms/mouse, i.c.v.) did not significantly modify the baclofen effect. 5. None of the K+ channel blockers tested (gliquidone, 8-16 micrograms/mouse; 4-AP, 25-250 ng/mouse and TEA, 10-20 micrograms/mouse, i.c.v.), significantly modified the antinociception induced by U50,488H (8 mg kg-1, s.c.). 6. These results suggest that the opening of K+ channels is involved in the antinociceptive effect of alpha 2 and GABAB, but not kappa-opioid, receptor agonists. The K+ channels opened by alpha2-adrenoceptor agonists seem to be ATP-dependent channels, whereas those opened by GABAB receptor agonists are not.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ocaña
authors.forename: J M
authors.initials: JM
authors.lastname: Baeyens
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D015761:4-Aminopyridine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009619:Nociceptors / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D015221:Potassium Channels; D011759:Pyrrolidines; D018341:Receptors, Adrenergic, alpha-2; D018079:Receptors, GABA; D017473:Receptors, Opioid, kappa; D013453:Sulfonylurea Compounds; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D015761:4-Aminopyridine; D001418:Baclofen; D003000:Clonidine