Kappa opioid receptor-mediated suppression of voltage-activated potassium current in a catecholaminergic neuronal cell line.
Opioid sensitivity of a catecholaminergic cell line (CATH.a) of brainstem origin was examined using whole-cell voltage-clamp techniques. Morphine produced a preferential and concentration-dependent decrease of the amplitude of voltage-activated potassium current, IK (ED50 = approximately 4 microM, maximum inhibition 52%, n = 33). The mu-selective opiate agonist [D-Ala2, MePhe, Gly-ol5] enkephalin (2-20 microM; n = 6) and the delta-selective agonist [D-Pen2, D-Pen5] enkephalin (2-20 microM; n = 7) produced no effect. However, the kappa-selective agonist trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)ben zene-acetamide reduced IK in a concentration-dependent manner (EC50 = 2.3 microM, maximum inhibition 44%, n = 40). The kappa receptor antagonist nor-binaltorphimine (10 nM) blocked the effect of either morphine (10 microM, n = 6) or U50,488 (10 microM, n = 7). Kappa agonist-mediated IK reduction was prevented by intracellular dialysis with an inactive form of guanosine diphosphate, guanosine 5'-O-(2-thio)diphosphate (100-200 microM; n = 10) but was unchanged by incubation with pertussis toxin (500 ng/ml, 24-48 h, n = 10). These results suggest that opioid suppression of IK is mediated by kappa-opioid receptors coupled to a pertussis toxin-insensitive G-protein.
Baraban
S C
SC
Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, USA.
Lothman
E W
EW
Lee
A
A
Guyenet
P G
PG
D002395:Catecholamines / Q000378:metabolism*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism; D015640:Ion Channel Gating; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000819:agonists / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism*
D002395:Catecholamines; D009294:Narcotics; D015221:Potassium Channels; D017473:Receptors, Opioid, kappa; D009020:Morphine; D019204:GTP-Binding Proteins