Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation.
Using an in vitro neonatal rat gastric-brainstem preparation, the activity of majority neurons recorded in the nucleus tractus solitarius (NTS) of the brainstem were significantly inhibited by GABA A receptor agonist, muscimol (30 microM), and this inhibition was reversed by selective GABA A receptor antagonist, bicuculline (10 microM). Application of kavalactones (300 microg/ml) and dihydrokavain (300 microM) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (39 % and 32 %, respectively, compared to the control level), and this reduction was partially reversed by bicuculline (10 microM). Kavalactones or dihydrokavain induced inhibitory effects were not reduced after co-application of saclofen (10 microM; a selective GABA B receptor antagonist) or naloxone (100 nM; an opioid receptor antagonist). Pretreatment with kavalactones (300 microg/ml) or dihydrokavain (300 microM) significantly decreased the NTS inhibitory effects induced by muscimol (30 microM), approximately from 51 % to 36 %. Our results demonstrated modulation of brainstem GABAergic mechanism by kavalactones and dihydrokavain, and suggested that these compounds may play an important role in regulation of GABAergic neurotransmission.
Yuan
Chun-Su
CS
Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago 60637, USA. cyuan@midway.uchicago.edu
Dey
Lucy
L
Wang
Anbao
A
Mehendale
Sangeeta
S
Xie
Jing-Tian
JT
Aung
Han H
HH
Ang-Lee
Michael K
MK
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D018682:GABA Agents / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D020901:Kava; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects*
D018682:GABA Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D007783:Lactones; D009292:Narcotic Antagonists; D010936:Plant Extracts; D011753:Pyrones; D009118:Muscimol; D009270:Naloxone; C113859:dihydrokavain; D001418:Baclofen; C080629:saclofen