Obovatol isolated from Magnolia obovata enhances pentobarbital-induced sleeping time: Possible involvement of GABAA receptors/chloride channel activation.
This study aimed to investigate the effects of obovatol isolated from Magnolia obovata on pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by GABA(A) receptors/chloride channel activation, using a western blot technique and Cl(-) sensitive fluorescence probe. GABA(A) receptors subunits expression and chloride influx were investigated in cultured cerebellar granule cells. Obovatol (0.05, 0.1, and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg). In addition, obovatol (20 and 50 microM) significantly increased Cl(-) influx in the primary cultured cerebellar granule cells. Moreover, obovatol increased the expression of GABA(A) receptor alpha-, beta-, and gamma-subunits. However, it had no effect on the abundance of the expression of glutamic acid decarboxylase (GAD), suggesting that obovatol might not activate GAD. These results suggest that obovatol potentiates pentobarbital-induced sleeping time through the GABA(A) receptors/chloride channel activation.
Ma
Hong
H
College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
Jo
Young-Jun
YJ
Ma
Yuan
Y
Hong
Jin-Tae
JT
Kwon
Byoung-Mog
BM
Oh
Ki-Wan
KW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism*; D018757:GABA Modulators / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D031566:Magnolia / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D010647:Phenyl Ethers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves; D011963:Receptors, GABA-A / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects*
D001713:Biphenyl Compounds; D018118:Chloride Channels; D018757:GABA Modulators; D010647:Phenyl Ethers; D010936:Plant Extracts; D011963:Receptors, GABA-A; C036795:obovatol; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D010424:Pentobarbital