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Hippocampal Membranes (hippocampal + membrane)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

5-HT1A RECEPTOR AGONIST PROPERTIES OF ANTIPSYCHOTICS DETERMINED BY [35S]GTP,S BINDING IN RAT HIPPOCAMPAL MEMBRANES

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2007
Yuji Odagaki
SUMMARY 15-Hydroxytryptamine 1A (5-HT1A) receptors have attracted increasing attention as a promising target for antipsychotic therapy. Although many atypical antipsychotic drugs, including the prototype clozapine, have been reported to be partial agonists at 5-HT1A receptors, these results are often fragmental and derived mainly from experiments that used cultured cells. 2In the present study, [35S]guanosine 5,- O -(3-thiotriphosphate) ([35S]GTP,S) binding assay in rat hippocampal membranes was applied to a series of antipsychotic drugs, especially atypical antipsychotics. 3Most, but not all, of atypical antipsychotic drugs and the classical antipsychotic drug nemonapride behaved as partial agonists at 5-HT1A receptors with varied potencies and relative efficacies. The most potent compound was perospirone with a mean EC50 of 27 nmol/L, followed by aripiprazole (45 nmol/L) > ziprasidone (480 nmol/L) > nemonapride (790 nmol/L) > clozapine (3900 nmol/L) > quetiapine (26 000 nmol/L). The maximal percentage increases over the basal binding (%Emax) for these antipsychotic drugs were 30,50%, with the exception of perospirone (, 15%), whereas 5-HT stimulated the binding to a mean %Emax of 105%. 4Increasing concentrations of the selective and neutral 5-HT1A antagonist WAY100635 shifted the concentration,response curve of nemonapride-stimulated [35S]GTP,S binding to the right and in parallel. 5The relative efficacy or intrinsic activity of a compound was affected differently by the differing concentrations of guanosine diphosphate (GDP) in the assay buffer, which should be taken into consideration when determining the relative efficacies of these antipsychotics as 5-HT1A receptor agonists. 6These results provide important information concerning the relevance of 5-HT1A receptor partial agonist properties in the treatment for schizophrenic patients with most, if not all, of atypical antipsychotic drugs. [source]

Adenosine A3 receptors in the rat hippocampus: Lack of interaction with A1 receptors

DRUG DEVELOPMENT RESEARCH, Issue 4 2003
Luísa V. Lopes
Abstract Adenosine acts as a neuromodulator in the hippocampus essentially through activation of inhibitory A1 receptors. Using single-cell PCR analysis, we found that CA1 pyramidal cells coexpress A1 receptor mRNA together with that of another adenosine receptor, the A3 receptor. As occurs for the A1 receptor, Western blot analysis indicated that the A3 receptor is also located in hippocampal nerve terminals. However, activation of A3 receptors with its purportedly selective agonist Cl-IBMECA (0.1,10 µM) failed to affect hippocampal synaptic transmission or to modify the evoked release of glutamate or GABA. Also, blockade of A3 receptors with MRS 1191 (5 µM) failed to affect either hypoxia- or ischemia-induced depression of hippocampal synaptic transmission. Activation of A3 receptors also failed to control A1 receptor function, as Cl-IBMECA (100 nM) did not modify the ability of CPA to displace [3H]DPCPX binding to hippocampal membranes or the A1 receptor-mediated inhibition of hippocampal synaptic transmission. However, ligand binding studies revealed that Cl-IBMECA displaced the binding of an A1 receptor agonist ([3H]R-PIA, Ki=47 nM) or antagonist ([3H]DPCPX, Ki=130 nM), which suggests that A3 receptor ligands also act on native A1 receptors. We believe that A3 receptors are expressed in hippocampal neurons and are located in hippocampal nerve terminals, though their function remains elusive. Drug Dev. Res. 58:428,438, 2003. © 2003 Wiley-Liss, Inc. [source]

Acutely administered melatonin decreases somatostatin-binding sites and the inhibitory effect of somatostatin on adenylyl cyclase activity in the rat hippocampus

JOURNAL OF PINEAL RESEARCH, Issue 2 2004
Rosa María Izquierdo-Claros
Abstract:, Melatonin is known to increase neuronal activity in the hippocampus, an effect contrary to that of somatostatin (somatotropin release-inhibiting factor, SRIF). Thus, the aim of this study was to investigate whether the somatostatinergic system is implicated in the mechanism of action of melatonin in the rat hippocampus. One group of rats was injected a single dose of melatonin [25 ,g/kg subcutaneously (s.c.)] or saline containing ethanol (0.5%, s.c.) and killed 5 hr later. Melatonin significantly decreased the SRIF-like immunoreactivity levels and induced a significant decrease in the density of SRIF receptors as well as in the dissociation constant (Kd). SRIF-mediated inhibition of basal and forskolin-stimulated adenylyl cyclase activity was markedly decreased in hippocampal membranes from melatonin-treated rats. The functional activity of Gi proteins was similar in hippocampal membranes from melatonin-treated and control rats. Western blot analyses revealed that melatonin administration did not alter Gi,1 or Gi,2 levels. To determine if the changes observed were related to melatonin-induced activation of central melatonin receptors, a melatonin receptor antagonist, luzindole, was administered prior to melatonin injection. Pretreatment with luzindole (10 mg/kg, s.c.) did not alter the melatonin-induced effects on the above-mentioned parameters and luzindole, alone, had no observable effect. The present results demonstrate that melatonin decreases the activity of the SRIF receptor,effector system in the rat hippocampus, an effect which is apparently not mediated by melatonin receptors. As SRIF exerts an opposite effect to that of melatonin on hippocampal neuronal activity, it is possible that the SRIFergic system could be implicated in the mechanism of action of melatonin in the rat. [source]