RESUMEN
Valeriana officinalis (valerian) is used traditionally as a mild sedative. Research into valerian is sparse, and studies differ greatly with respect to design, measures and preparations used. This study compares the action of a methanol (M-E), ethanol (E-E) and an extract macerated with ethylacetate (EA-E) from roots of valerian (Valeriana officinalis L., Valerianaceae) on postsynaptic potentials (PSPs) in cortical neurons. Intracellular recordings were performed in rat brain slice preparations containing pyramidal cells of the cingulate cortex. PSPs were induced by electrical field stimulation. The M-E induced strong inhibition in the concentration range 0.1-15 mg/mL, whereas the E-E (1-10 mg/mL) did not influence significantly the PSPs. The maximum inhibition induced by the M-E was completely antagonized by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microm), an antagonist on the adenosine A(1) receptor. Contrary to the M-E, the EA-E (10 mg/mL) induced an increase of the PSPs, which was completely blocked by the GABA(A) receptor antagonist picrotoxin (100 microm). The data suggest that activation of adenosine A(1) and GABA(A) receptors is mediated by different components within the valerian extract. The two mechanisms may contribute independently to the sleep-inducing effect of valerian.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Neuronas/efectos de los fármacos , Receptor de Adenosina A1/fisiología , Receptores de GABA-A/fisiología , Transmisión Sináptica/efectos de los fármacos , Valeriana/química , Animales , Corteza Cerebral/citología , Etanol/química , Masculino , Potenciales de la Membrana/efectos de los fármacos , Metanol/química , Neuronas/fisiología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Ratas , Ratas WistarRESUMEN
In this study we evaluated the adenosine A1 receptor-mediated effect of valerian extract (Ze 911) on postsynaptic potentials (PSPs) in pyramidal cells of the rat cingulate cortex in a slice preparation. We first observed that N6-cyclopentyladenosine (CPA, 0.01 - 10 microM), an adenosine A1 receptor agonist, inhibited PSPs in a concentration-dependent manner. The CPA (10 microM)-induced inhibition was antagonized by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microM), an adenosine A1 receptor antagonist. Ze 911 concentration dependently (0.1 - 15 mg/mL) inhibited PSPs in the presence of the adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC, 0.2 microM) and adenosine deaminase (1 U/mL). The maximal inhibition induced by 10 mg/mL was completely antagonised by DPCPX (0.1 microM), an A1 receptor blocker. The data suggest that activation of adenosine A1 receptors is involved in the pharmacological effects of the valerian extract Ze 911.
Asunto(s)
Potenciales Postsinápticos Excitadores/efectos de los fármacos , Extractos Vegetales/farmacología , Células Piramidales/efectos de los fármacos , Receptor de Adenosina A1/efectos de los fármacos , Valeriana , Agonistas del Receptor de Adenosina A1 , Animales , Giro del Cíngulo/citología , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Células Piramidales/fisiología , Ratas , Ratas WistarRESUMEN
Intracellular recordings were made in rat brain slice preparations containing pyramidal cells of the associative frontal cortex in order to characterize the action of selective adenosine A(1) and A(3) receptor ligands on synaptic neurotransmission. The selective A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) inhibited concentration-dependently the excitatory postsynaptic potentials (PSPs) which were evoked by focal electrical stimulation. The CPA-mediated inhibition was blocked by 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX), a highly A(1) receptor-selective antagonist. The A(3) receptor agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) inhibited concentration-dependently the evoked PSPs while the A(1) receptors were blocked continuously by DPCPX. Under these conditions, the A(3) receptor antagonist 9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino]-1,2,4-triazolo[1, 5-c]quinazoline (MRS 1220) did not influence the PSPs but inhibited completely the effect of IB-MECA. The inhibitory effect of IB-MECA was unaffected by DPCPX. CPA additionally inhibited the PSPs when applied after IB-MECA. Pharmacological dissociation of the N-methyl-D-aspartate (NMDA) and non-NMDA receptor components of the PSPs showed that CPA as well as IB-MECA reduced both. We conclude that adenosine A(1) and A(3) receptors are present on cortical pyramidal cells and involved in the inhibition of excitatory neurotransmission. Our results indicate no interplay between the two receptor subtypes. The separate inhibition may become particularly evident in situations where there are high levels of endogenously released adenosine, as seen in hypoxia.