Cyclopeptide alkaloid fraction from Zizyphi Spinosi Semen enhances pentobarbital-induced sleeping behaviors.
This study aimed to investigate effects of cyclopeptide alkaloid fraction of ZSS (CAFZ) on pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by gamma-aminobutyric acid (GABA) receptors Cl(-) channel activation, using a Western blot technique and Cl(-) sensitive fluorescence probe. GABA receptors subunits expression and Cl(-) influx were investigated in cultured cerebellar granule cells. CAFZ shortened sleeping onset and prolonged sleeping time induced by pentobarbital (42 mg/kg). It also significantly increased the falling asleep rate and duration of sleeping time at a sub-hypnotic dosage of pentobarbital (28 mg/kg). In addition, CAFZ in combination with GABA A receptors agonist, muscimol, synergistically prolonged pentobarbital-induced sleeping time. Both of CAFZ and pentobarbital treatment decreased GABA A receptors alpha-subunit expression, but did not change beta- and gamma-subunit expression. However, we found CAFZ and pentobarbital increased Cl(-) influx, CAFZ showed similar effects with muscimol in potentiating Cl(-) influx inducing effects of low-dose pentobarbital. In conclusion, it is suggested that the enhancement of Cl(-) influx by CAFZ may play an important role in the potentiation of pentobarbital-induced sleeping behaviors.
Ma
Yuan
Y
College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, South Korea.
Han
Huishan
H
Nam
Sang-Yoon
SY
Kim
Yun-Bae
YB
Hong
Jin-Tae
JT
Yun
Yeo-Pyo
YP
Oh
Ki-Wan
KW
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D004357:Drug Synergism; D018755:GABA Agonists / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis; D012890:Sleep / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D031957:Ziziphus / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000470:Alkaloids; D002712:Chlorides; D018755:GABA Agonists; D006993:Hypnotics and Sedatives; D010936:Plant Extracts; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010424:Pentobarbital