Selective antagonists at serotonin 5-HT receptors (5-HTR) improve memory performance in rodents and are currently under clinical investigations. If blockade of 5-HTR is known to increase glutamate release, only two studies have so far demonstrated an interaction between 5-HTR and glutamate transmission, but both, using the non-competitive NMDA antagonist MK-801, insensitive to variations of glutamate concentrations. In a place recognition task, we investigated here in mice the role of glutamate transmission in the beneficial effects of 5-HTR blockade (SB-271046).
View Article and Find Full Text PDFBased on the definition of a 5-HT(4) receptor antagonist pharmacophore, a series of pyrrolo[1,2-a]thieno[3,2-e] and pyrrolo[1,2-a]thieno[2,3-e] pyrazine derivatives were designed, prepared, and evaluated to determine the properties necessary for high-affinity binding to 5-HT(4) receptors. The compounds were synthesized by substituting the chlorine atom of the pyrazine ring with various N-alkyl-4-piperidinylmethanolates. They were evaluated in binding assays with [(3)H]GR113808 (1) as the 5-HT(4) receptor radioligand.
View Article and Find Full Text PDFStudies have recently suggested that blockade of 5-HT6 receptors (5-HT6R) improves memory processes. As episodic memory alteration is one of the first deficits observed during normal aging and in neurological and neuropsychiatric disorders (Alzheimer's disease, schizophrenia), the present study sought to characterize the effects of 5-HT6R blockade on spatial recognition memory, which can be considered as 'episodic-like' memory, in rodents. We quantified the effects of the selective 5-HT6R antagonist SB-271046 (10 mg/kg, i.
View Article and Find Full Text PDFBone-marrow-derived mesenchymal stem cells (MSCs) constitute an interesting cellular source to promote brain regeneration after neurodegenerative diseases. Recently, several studies suggested that oxygen-dependent gene expression is of crucial importance in governing the essential steps of neurogenesis such as cell proliferation, survival and differentiation. In this context, we analysed the effect of the HIF-1 (hypoxia inducible factor-1) activation-mimicking agent CoCl(2) on MSCs.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
November 2002
We studied the cellular phosphatase inhibitors okadaic acid (OKA), calyculin A, and microcystin on the epithelial sodium channel (ENaC) in A6 renal cells. OKA increased the amiloride-sensitive current after approximately 30 min with maximal stimulation at 1-2 h. Fluctuation analysis of cell-attached patches containing a large number of ENaC yielded power spectra with corner frequencies in untreated cells almost two times as large as in cells pretreated for 30 min with OKA, implying an increase in single channel open probability (P(o)) that doubled after OKA.
View Article and Find Full Text PDFAim Of The Study: To evaluate the results of parathyroid scinti scans (sestamibi or tetrofosmin) for detection of hyperplastic parathyroid glands responsible for renal hyperparathyroidism.
Methods: Injection of 15 mCi sestamibi or tetrofosmin and gammacamera acquisition of images focused on neck and mediastinum, 20 minutes and 2 hours thereafter. Injection of 150 mCi Iodine 123, acquisition of images 2 hours afterwards and visual subtraction.
Recently, inhalation anesthetics have been reported to block BK channels in adrenal chromaffin cells. To determine if BK block was characteristic only of inhalation anesthetics or was also a property of other general anesthetics we examined the effects of ketamine, an intravenous general anesthetic which is structurally different than inhalation anesthetics. Cell-attached and excised patch single channel and standard whole cell recording techniques were used to examine the effect of racemic ketamine on the BK channel activity in GH3 cells.
View Article and Find Full Text PDFInsulin increases epithelial Na+ reabsorption, and many of its actions involve tyrosine kinase. We used tyrosine kinase inhibitors to examine the role of tyrosine kinase in the action of insulin. Pretreatment of Na+ transporting cells with tyrosine kinase inhibitors attenuates the subsequent action of insulin, suggesting that the action of insulin on epithelial Na+ transport involves tyrosine kinase activity.
View Article and Find Full Text PDFThe high selectivity, low conductance, amiloride-blockable, sodium channel of the mammalian distal nephron (i.e. cortical collecting tubule) is the site of discretionary regulation which allows maintainance of total body sodium balance.
View Article and Find Full Text PDF1. The effects of gonadotrophins (luteinizing hormone and human chorionic gonadotrophin) and cyclic AMP on ionic conductances were investigated using the tight-seal whole-cell recording technique in Leydig cells freshly isolated from nature rat testis by enzymatic treatment. 2.
View Article and Find Full Text PDFReprod Nutr Dev (1980)
May 1989
Using intracellular microelectrode recordings, it was observed that FSH caused the hyperpolarization of cultured Sertoli cells from the testis of 17-day old rats; this hyperpolarization was related to the activation of a Na/K pump and an increase in Na/Ca influx and K efflux. The effect was irreversible and mediated by cAMP. Some other results suggested an initial effect of FSH on the junctional complex between the Sertoli cells and then its calcium dependence.
View Article and Find Full Text PDFVoltage-clamped membrane currents have been investigated from whole-cell patch-clamp recordings performed on single Leydig cells isolated from the adult rat testis. Two outward membrane currents were evoked by depolarizing voltage steps. A potassium current was recorded in cells dialyzed with low (10(-9)-10(-8) M) calcium media.
View Article and Find Full Text PDFAnn Med Interne (Paris)
September 1980
Three cases of granulomatous nephropathy are reported. In two patients this was definitely related to a true renal sarcoidosis, while the third case raised the problem of the significance of an "isolated sarcoidosis nodule". The authors discuss the frequency, clinical symptoms, and pathological appearances of these renal lesions which reveal the presence of sarcoidosis, as well as the relationship between renal insufficiency and the parenchymatous lesions observed, and therapy.
View Article and Find Full Text PDFJ Urol Nephrol (Paris)
December 1978