Effects of K+ channel blockers and openers on antinociception induced by agonists of 5-HT1A receptors.
The modulation by K+ channel-acting drugs of the antinociceptive effect of several 5-HT1A receptor agonists was examined with the hot plate test in mice. All the 5-HT1A receptor agonists tested induced dose-dependent antinociception, the order of potency being (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) > buspirone > or = lesopitron > or = tandospirone. The blockers of ATP-sensitive K+ channels (KATP) gliquidone and glipizide (1-4 and 16-64 micrograms/mouse i.c.v., respectively) reduced the antinociceptive effect of 8-OH-DPAT, whereas cromakalim (32-64 micrograms/mouse i.c.v.), an opener of KATP channels, enhanced the effect. In contrast, 4-aminopyridine (25-250 ng/mouse i.c.v.) and tetraethylammonium (10-20 micrograms/mouse i.c.v.), which antagonize several non-ATP-dependent K+ conductances, were inactive. The same results were found with other agonists of 5-HT1A receptors (lesopitron, buspirone and tandospirone): gliquidone inhibited whereas cromakalim increased their antinociceptive effects. None of the K+ channel-acting drugs modified the binding of [3H]8-OH-DPAT to hippocampal membranes, whereas all the 5-HT1A receptor agonists displaced the ligand. These results suggest that ATP-sensitive K+ conductances are involved in the antinociception induced by agonists of 5-HT1A receptors.
Robles
L I
LI
Department of Pharmacology, University of Granada, Spain.
Barrios
M
M
Del Pozo
E
E
Dordal
A
A
Baeyens
J M
JM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010147:Pain Measurement; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000494:pharmacology
D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C010969:gliquidone