PALMITONE (AN ANTICONVULSANT DRUG) INCREASES [[sup3]H]FORSKOLIN BINDING IN MICE BRAIN. AN AUTORADIOGRAPHY STUDY
Abstract number :
2.129
Submission category :
Year :
2003
Submission ID :
576
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Eva Gonzalez, Magdalena Briones, Andres Navarrete, Leticia Neri, Luisa L. Rocha Subdireccion de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatria Ramon de la Fuente, D.F., Mexico, Mexico; Farmacia, Facultad de Quimica de la Universidad A
Palmitone is an aliphatic ketone that has shown anticonvulsant effect in several acute experimental models of epilepsy. It was isolated from the ethanol extract of [italic]Annona diversifolia [/italic] leaves, a native indigenous tree from Mexico. Although its mechanism of action is not very well known, its anticonvulsant effect has been associated with the activation of inhibitory systems. The present study was carried out to evaluate the effect of acute administration of palmitone in forskolin binding in mice brain trough an [italic]in vitro[/italic] autoradiography procedure.
Male Taconic mice (25-30 g) [italic]ad libitum[/italic] were used. Control group (n=6) received a vehicle injection (saline solution in tween 80, i.p. in a volume of 0.1 ml/10g of body weight). The experimental group was treated with 5 mg/kg of palmitone (n=6, i.p.). Animals were decapitated 24 h after injections and coronal brain frozen sections (20 [mu]m) were obtained and taken for autoradiography process using [3H]forskolin as ligand. The optical density (OD) was quantified using program JAVA, Jandel software of analysis of video. The mean of 10 lectures of OD was taken and converted to fmol/mg of tissue from tritium standards curve.
It was found that palmitone administration increased [3H]forskolin binding in several cerebral areas in comparison with control group. Increase was significantly in caudate putamen (58%), piriform (76%) and parietal (45%) cortices, CA1-3 areas from hippocampus (31%), anterior (39%), medial (32%) and central (54%) amygdaloid nuclei, thalamus (70%) and hypothalamus (70%) (p[lt]0.05).
Forskolin is a stimulating of adenylyl cyclase considered to be a transmembrane enzyme that catalyzes the formation of cAMP, one of the important intracellular second messengers. Studies reported that cAMP content increased until the seizures have occurred suggesting the possibility that an increase in cAMP may be involved in seizure attenuation. Because of this, our present experiments suggest that anticonvulsant effect of palmitone could involve the participation of this second messenger.
[Supported by: Instituto Nacional de Psiquiatria Ramon de la Fuente, Fundacion Miguel Aleman, A.C. and CONACyT 31702M.]