Involvement of chloride channel coupled GABA(C) receptors in the peripheral antinociceptive effect induced by GABA(C) receptor agonist cis-4-aminocrotonic acid.
We investigated the effect of chloride and potassium channel blockers on the antinociception induced by GABA(C) receptor agonist CACA (cis-4-aminocrotonic acid) using the paw pressure test, in which pain sensitivity was increased by an intraplantar injection (2 microg) of prostaglandin E(2) (PGE(2)). CACA administered locally into the right hindpaw (25, 50 and 100 microg/paw) elicited a dose-dependent antinociceptive effect which was demonstrated to be local, since only higher doses produced an effect when injected in the contralateral paw. The GABA(C) receptor antagonist (1,2,5,6 tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA; 5, 10 and 20 microg/paw) antagonized, in a dose-dependent manner, the peripheral antinociception induced by CACA (100 microg), suggesting a specific effect. This effect was reversed by the chloride channel coupled receptor blocker picrotoxin (0.8 microg/paw). Glibenclamide (160 microg) and tolbutamide (320 microg), blockers of ATP-sensitive potassium channels, charybdotoxin (2 microg), a large-conductance potassium channel blocker, dequalinium (50 microg), a small-conductance potassium channel blocker, and cesium (500 microg), a non-specific potassium channel blocker did not modify the peripheral antinociception induced by CACA. This study provides evidence that activation of GABA(C) receptors in the periphery induces antinociception, that this effect results from the activation of chloride channel coupled GABA(C) receptors and that potassium channels appear not to be involved.
Reis
Gláucia Maria Lopes
GM
Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, Belo Horizonte, Brazil.
Duarte
Igor Dimitri Gama
ID
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003437:Crotonates / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006614:Hindlimb; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010721:Phosphinic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018079:Receptors, GABA / Q000378:metabolism*
D000700:Analgesics; D003437:Crotonates; D015232:Dinoprostone; D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D010852:Picrotoxin; D026902:Potassium Channel Blockers; D011725:Pyridines; D018079:Receptors, GABA; C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; C087200:GABA-C receptor; C055331:4-aminocrotonic acid