U50488 inhibits outwardly rectifying potassium channel in PC12 cells via pertussis toxin-sensitive G-protein.
This study was undertaken to determine the effect of U50488, a kappa-opioid receptor agonist, on outwardly rectifying potassium channel (Ik) in undifferentiated PC12 cells. Using whole-cell and on-cell patch-clamp techniques, we found that U50488 decreased Ik amplitude in a time-dependent manner and Ik activation was delayed. Single-channel kinetic analysis provided a two-stage model for us to illuminate the blockage effect induced by U50488. To identify whether U50488 mediates the effect through opioid receptor and G-protein, several specific blockers and activators were used. Not only naloxone but also PTX and GDPbetaS abolished U50488-induced suppression; however, such effect was not observed when cAMP or other adenylyl cyclase activators were used. It is postulated that kappa-opioid receptor and Gi/o protein, but not cAMP, are involved in U50488-induced suppression of Ik.
Li
Zhisong
Z
Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Guo
Lei
L
Ye
Caiying
C
Zhang
Dechang
D
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000378:metabolism*
D004338:Drug Combinations; D015221:Potassium Channels; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins