Planta Med 2002; 68(12): 1092-1096
DOI: 10.1055/s-2002-36338
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Kavalactones and Dihydrokavain Modulate GABAergic Activity in a Rat Gastric-Brainstem Preparation

Chun-Su Yuan1, 2, 3 , Lucy Dey1, 3 , Anbao Wang1, 3 , Sangeeta Mehendale1, 3 , Jing-Tian Xie1, 3 , Han H. Aung1, 3 , Michael K. Ang-Lee3
  • 1Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago, U.S.A.
  • 2Committee on Clinical Pharmacology, The Pritzker School of Medicine, University of Chicago, Chicago, U.S.A.
  • 3Department of Anesthesia & Critical Care, The Pritzker School of Medicine, University of Chicago, Chicago, U.S.A.
Further Information

Publication History

Received: March 8, 2002

Accepted: June 29, 2002

Publication Date:
20 December 2002 (online)

Abstract

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 GABAA receptor agonist, muscimol (30 μM), and this inhibition was reversed by selective GABAA receptor antagonist, bicuculline (10 μM). Application of kavalactones (300 μg/ml) and dihydrokavain (300 μM) 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 μM). Kavalactones or dihydrokavain induced inhibitory effects were not reduced after co-application of saclofen (10 μM; a selective GABAB receptor antagonist) or naloxone (100 nM; an opioid receptor antagonist). Pretreatment with kavalactones (300 μg/ml) or dihydrokavain (300 μM) significantly decreased the NTS inhibitory effects induced by muscimol (30 μM), 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.

References

Chun-Su Yuan, MD PhD

Department of Anesthesia & Critical Care

The Pritzker School of Medicine

University of Chicago

5841 S. Maryland Avenue, MC 4028

Chicago, Illinois 60637

U.S.A.

Phone: +1-773-702-1916

Fax: +1-773-834-0601

Email: cyuan@midway.uchicago.edu

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