Mixed antagonistic effects of bilobalide at rho1 GABAC receptor.
Bilobalide was found to be a moderately potent antagonist with a weak use-dependent effect at recombinant human rho(1) GABA(C) receptors expressed in Xenopus oocytes using two-electrode voltage clamp methodology. Antagonism of bilobalide at homomeric rho(1) GABA(C) receptors appeared to be mixed. At low concentration, bilobalide (3 microM) caused a parallel right shift and surmountable GABA maximal response of the GABA dose-response curve characteristic of a competitive antagonist. At high concentrations, bilobalide (10-100 microM) caused nonparallel right shifts and reduced maximal GABA responses of GABA dose-response curves characteristic of a noncompetitive antagonist. The potency of bilobalide appears to be dependent on the concentrations of GABA and was more potent at lower GABA concentrations. The mechanism of action of bilobalide at rho(1) GABA(C) receptors appears to be similar to that of the chloride channel blocker picrotoxinin.
Huang
S H
SH
Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology D06, Faculty of Medicine, The University of Sydney, NSW 2006, Australia.
Duke
R K
RK
Chebib
M
M
Sasaki
K
K
Wada
K
K
Johnston
G A R
GA
D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005663:Furans / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D018014:Gene Transfer Techniques; D046934:Ginkgolides; D006801:Humans; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D021122:Protein Subunits / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D018118:Chloride Channels; D003517:Cyclopentanes; D004224:Diterpenes; D005663:Furans; D018756:GABA Antagonists; D046934:Ginkgolides; D010852:Picrotoxin; D010936:Plant Extracts; D021122:Protein Subunits; D018079:Receptors, GABA; D011993:Recombinant Fusion Proteins; D005680:gamma-Aminobutyric Acid; C087200:GABA-C receptor; C073710:bilobalide