Riluzole attenuates the effects of chemoconvulsants acting on glutamatergic and GABAergic neurotransmission in the planarian Dugesia tigrina

详细信息    查看全文

• 作者：Latha Ramakrishnan ; Zachary Dalhoff ; Samantha L. Fettig ; Michael R. Eggerichs ; Briegette E. Nelson ; Bibita Shrestha ; Amira H. Elshikh ; Pratima Karki
• 关键词：L-Glutamate (PubChem CID ; 33032) ; 纬-Aminobutyric acid (PubChem CID ; 119) ; Riluzole hydrochloride (PubChem CID ; 6419992) ; Semicarbazide hydrochloride (PubChem CID ; 11236) ; Dizocilpine maleate (PubChem CID ; 1207) ; N-Methyl-D-aspartate (PubChem CID ; 22880) ; 2 ; 3-Naphthalene dicarboxaldehyde (PubChem CID ; 96400)
• 刊名：European Journal of Pharmacology
• 出版年：15 October, 2013
• 年：2013
• 卷：718
• 期：1-3
• 页码：493-501
• 全文大小：972 K

文摘

Planarians, the non-parasitic flatworms, display dose-dependent, distinct (C-like and corkscrew-like) hyperkinesias upon exposure to 0.001-10 mM aqueous solutions of glutamatergic agonists (l-glutamate and N-methyl-d-aspartate (NMDA)) and 0.001-5 mM concentrations of the glutamate decarboxylase (GAD) inhibitor (semicarbazide). In the planarian seizure-like activity (PSLA) experiments the three chemoconvulsants displayed the following order of potency (EC₅₀): l-glutamate (0.6 mM)>NMDA (1.4 mM)>semicarbazide (4.5 mM). Planarian hyperkinesias behavior counting experiments also revealed that riluzole (0.001 to 1 mM), an anti-convulsive agent, displayed no significant behavioral activity by itself, but attenuated hyperkinesias elicited by the three chemoconvulsants targeting either glutamatergic or GABAergic neurotransmission with the following order of potency (IC₅₀): NMDA (44.7 碌M)>semicarbazide (88.3 碌M)>l-glutamate (160 碌M). Further, (+)-MK-801, a specific NMDA antagonist, alleviated 3 mM NMDA (47%) or 3 mM l-glutamate (27%) induced planarian hyperkinesias. The results provide pharmacological evidence for the presence of glutamatergic receptor-like and semicarbazide sensitive functional GAD enzyme-like proteins in planaria in addition to demonstrating, for the first time, the anti-convulsive effects of riluzole in an invertebrate model. High performance liquid chromatography coupled with fluorescence detection (HPLC-F) analysis performed on planarian extracts post no drug treatment (control) or treatment with 3 mM semicarbazide, combination of 3 mM semicarbazide and 0.1 mM riluzole, or 0.1 mM riluzole revealed that 3 mM semicarbazide induced 35% decrease in the GABA levels and a combination of 3 mM semicarbazide and 0.1 mM riluzole induced 42% decrease in glutamate levels with respect to the control group.