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H Daniel

Publications and source records attributed to H Daniel.

At least 91 records · Page 5Linked to original sources
PubMed1994

Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1.

Metabotropic glutamate receptor 1 (mGluR1) is a member of a large family of G-protein-coupled glutamate receptors, the physiological functions of which are largely unknown. Mice deficient in mGluR1 have severe motor coordination and spatial learning deficits. They have no gross anatomical or basic electrophysiological abnormalities in either the cerebellum or hippocampus, but they show impaired cerebellar long-term depression and hippocampal mossy fibre long-term potentiation. mGluR1-deficient mice should therefore be valuable models for studying synaptic plasticity.

Animals↗
PubMed1994

Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, beta-lactam antibiotics and ACE-inhibitors.

Injection of poly(A)+ RNA from rabbit small intestine into Xenopus laevis oocytes resulted in expression of pH dependent transport of the aminocephalosporin cefadroxil. A cDNA library constructed from a 2.2 to 5 kb fraction was screened for expression of cefadroxil transport after injection of the corresponding cRNA synthetized in vitro from different pools of clones. The single clone identified stimulated uptake of cefadroxil into oocytes about 50-fold at pH 6.5. Kinetic analysis of expressed transport activity revealed a saturable transport system shared by amino beta-lactam antibiotics, dipeptides and selected angiotensin converting enzyme inhibitors. Evidence for rheogenic cefadroxil/H(+)-cotransport was obtained by a) The demonstration that cefadroxil influx increased the inward current in oocytes clamped at a holding potential of -60 mV in sodium-free medium and b) A decrease of intracellular pH in oocytes caused by cefadroxil uptake. Current-voltage relationships in the presence of glycylsarcosine or cefadroxil showed that transport activity is dependent on the membrane potential. Sequencing of the cDNA revealed its identity with the recently cloned peptide transporter from rabbit small intestine designated PepT1.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Cellular locus of the nitric oxide-synthase involved in cerebellar long-term depression induced by high external potassium concentration.

The cellular location of the NO-synthase involved in long-term depression (LTD) of parallel fiber (PF)-mediated EPSCs induced by raising the external potassium (K) concentration has been investigated by using both whole-cell patch-clamp recordings (WCR) of Purkinje cells (PCs) in thin slices in vitro, and reverse transcription followed by polymerase chain reaction (PCR) applied to mRNAs harvested from these single PCs during WCR. In all tested cells in the control group, a large LTD of PF-mediated EPSCs was induced by perfusing the slices for 3 min with a high (30 mM) K perfusing medium. In a second group of cells for which the protein kinase C (PKC) inhibitor peptide 19-36 was added to the intrapipette solution at a concentration of 10 microM, the LTD following complete wash out of the high K solution was significantly less prominent than in the control group. Very similar results were also obtained when 30 microM NG-methyl-L-arginine (L-NMMA) was added to the perfusing medium. In contrast, when both the PKC inhibitor peptide 19-36 and L-NMMA were added to the intrapipette solution at a concentration of 10 and 30 microM respectively, no LTD was revealed following wash out of the high K solution. Finally, the PCR amplification of mRNAs harvested from these single PCs during WCR, as well as from granule cells from the same slices, confirms that mRNAs encoding the NO-synthase are expressed by granule cells, whereas they are not detected in PCs.

Amino Acid Oxidoreductases↗
PubMed1994

Properties of glutamate receptors are modified during long-term depression in rat cerebellar Purkinje cells.

Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell (PC) synapses occurs when these synapses are activated in conjunction with direct activation of voltage-gated calcium (Ca2+) channels of PCs. In the present study, we have used Aniracetam to test whether the expression of LTD at PF-PC synapses is due to a genuine modification of properties of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptors of these neurons. Whole-cell recordings of PF-mediated EPSCs were performed in thin slices taken from 16-22-day-old rats. In all tested cells, bath application of Aniracetam potentiated PF-mediated EPSCs and prolonged their decay without notably changing their rising phase. On the other hand, Aniracetam prevented the induction of LTD by a pairing protocol with Ca2+ spikes and, conversely, the nootropic compound had a larger potentiating effect on PF-mediated EPSCs during expression of LTD than normally, when this change in synaptic efficacy had been induced prior to Aniracetam application. These data strongly suggest that LTD involves a desensitization of postsynaptic AMPA receptors at PF-PC synapses, or, at least, a change in their functional characteristics.

Animals↗
PubMed1994

Rapid postabsorptive metabolism of nicotinic acid in rat small intestine may affect transport by metabolic trapping.

Postabsorptive metabolism of [3H]nicotinic acid by rat proximal jejunum was studied in vitro using the everted sac technique and in vivo by applying ligated loops. Metabolites were analyzed by HPLC with radiochemical detection. Within 60 min of incubation nicotinic acid was almost completely metabolized in vivo. Only 3.2% of the label could be detected in the original substrate nicotinic acid, whereas > 90% of the radioactivity present in the gut wall was nicotinamide. Further in vitro experiments revealed that conversion was rapid; after 10 min of incubation > 40% of the substrate was converted to other metabolites. From analysis of the serosal fluid, it was evident that only nicotinic acid and nicotinamide were transferred to the serosal compartment. Rapid conversion of nicotinic acid might affect the transport step itself by metabolic trapping, resulting in the maintenance of a substrate gradient necessary for passive absorption. In contrast, as examined by gradient centrifugation, the substrate in subcellular organelles is transferred only to a minor extent.

Animals↗
PubMed1994

Functional separation of dipeptide transport and hydrolysis in kidney brush border membrane vesicles.

Dipeptides serve as substrates for both transport and hydrolytic processes. This has caused uncertainty as to whether different systems mediate both processes, and if so, whether they can be functionally separated. To investigate these problems, we determined the effects of a series of compounds previously characterized as aminopeptidase (AP) inhibitors on transport and hydrolytic activities of the kidney brush border membrane. The substrate used for assaying transport activity was Gly-Gln whereas Leu-, Arg-, and Glu-nitroanilides, as well as Gly-Tyr and Ala-Tyr, were used in assaying hydrolytic activity. The AP inhibitors, arphamenines A and B and bestatin, strongly inhibited transport by the oligopeptide/H+ symporter (EC50 values of 15 to 67 microM). The mechanism of inhibition appeared to be competition for the binding site of the symporter. In contrast, leucinethiol, leuhistin, and amastatin had little or no effect on dipeptide transport (EC50 values of 4 to more than 50 mM). Arphamenine and leucinethiol, in concentrations as high as 100 microM, were found to be either ineffective or weak inhibitors of membrane-associated hydrolysis. In contrast, amastatin and leuhistin, in concentrations as low as 20 microM, almost completely inhibited dipeptide hydrolysis. These results show that dipeptide hydrolysis can be selectively suppressed by either amastatin or leuhistin and dipeptide transport by arphamenine. Furthermore, the results provide new insight into the structural features of substrates that are recognized at the binding site of the oligopeptide/H+ symporter.

Aminopeptidases↗
PubMed1994

Transport of cefadroxil in rat kidney brush-border membranes is mediated by two electrogenic H+-coupled systems.

The transport characteristics of the aminocephalosporin [3H]cefadroxil have been studied in brush-border membrane vesicles (BBMV) of rat kidney cortex by a rapid filtration technique and by use of a potential sensitive fluorescent dye. Influx of [3H]cefadroxil (0.25 microM) into BBMV as a function of time displayed a pronounced overshoot phenomenon in the presence of a transmembrane pH gradient (pHin > pHout). Evidence for an electrogenic cefadroxil/H+-symport in the presence of an inwardly directed proton gradient is provided by the demonstration of: 1) reduced uptake in the presence of a protonophore; 2) reduced uptake under voltage clamp conditions; and 3) increased uptake in the presence of a valinomycin-induced inside negative K+-diffusion potential. pH-gradient dependent uptake of [3H]cefadroxil as a function of substrate concentration revealed the presence of multiple carrier systems. By kinetic analysis, a high-affinity carrier system (Km, 8.8 +/- 1.3 microM) and a low-affinity system (Km, 2.62 +/- 0.80 mM) could be resolved. The high-affinity transport system was found to be very specific for substrates (cephalosporins and di- and tripeptides) carrying an alpha-amino group. By use of a potential sensitive fluorescent dye 3,3'-dipropylthiadicarbocyanine iodide, the low-affinity transport system was characterized with respect to its driving force and its kinetic features. This transporter was found also to be electrogenic in nature, representing a second cefadroxil/H+-symport system. In summary, our studies demonstrate for the first time uphill transport of cefadroxil in kidney BBMV mediated by multiple carrier systems. Transport is rheogenic, energized by the proton motive force and shared by other aminocephalosporins as well as di- and tripeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Long-term depression requires nitric oxide and guanosine 3':5' cyclic monophosphate production in rat cerebellar Purkinje cells.

In patch-clamped Purkinje cells, bath application of the nitric oxide synthase inhibitor NG-methyl-L-arginine consistently prevents the induction of long-term depression (LTD) of parallel fibre-mediated excitatory postsynaptic potentials (EPSPs) induced by their pairing with calcium spikes. On the other hand, bath application of nitric oxide donors and of 8-bromoguanosine 3':5' cyclic monophosphate is able to reproduce an LTD-like phenomenon. LTD of parallel fibre-mediated EPSPs also occurs when nitric oxide donors or guanosine 3':5' cyclic monophosphate are directly dialysed into Purkinje cells, and this effect partially occludes LTD induced by pairing protocols. These results show that nitric oxide does play a role in LTD induction, and demonstrate for the first time that its site of action is probably the soluble guanylate cyclase of Purkinje cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Removal of glycylglutamine from plasma by individual tissues: mechanism and impact on amino acid fluxes in postabsorption and starvation.

A possible source of glutamine, for inclusion in the parenteral solutions, is glycylglutamine. The aim of this article is to review briefly the information on metabolism of glycylglutamine when administered intravenously. The fact that there is efficient utilization of intravenously infused glycylglutamine was evident with very little excretion in the urine. Although all the tissues examined, except brain, participated in the removal of glycylglutamine from plasma, kidney predominated in this regard. This may be related to the presence of carrier-mediated systems for cellular uptake of glycylglutamine in the kidney and the lack of them in other tissues. Starvation did not alter the metabolic clearance of glycylglutamine, although it reduced the removal by the kidney. Renal metabolism of glycylglutamine resulted in the release of constituent amino acids that were largely utilized by the liver in the postabsorptive state and by skeletal muscle in starvation. This alteration was accompanied by a selective inhibition of muscle release of amino acids that are substrates for enhanced hepatic gluconeogenesis and renal ammoniagenesis in starvation. Because there was no change either in plasma glucose level or ammonia excretion during the infusion of glycylglutamine in starved human subjects, apparently the amino acid residues of glycylglutamine fulfilled the substrate needs for these functions. These results provide a metabolic basis for further investigations of the possible nutritional benefit of including glycylglutamine in parenteral nutrition.

Amino Acids↗
PubMed1993

Effects of phosphorylation of chrysotile on pleuropulmonary fibrogenicity and carcinogenicity.

As well as fibre size, fibre chemistry is a determinant of toxicity of mineral fibres. On these grounds, a few years ago, the asbestos industry in Québec developed a process to modify the surface chemistry of chrysotile asbestos by fixing phosphorous atoms. The pleuropulmonary fibrogenicity and carcinogenicity of the native and surface treated chrysotile, called chrysophosphate, were tested. Both products initiated similar pulmonary fibrogenicity in rats exposed by inhalation and sheep exposed by injection in the tracheal lobe. Tumour production in rats after long term inhalation or intrapleural injection was not different between chrysotile and chrysophosphate. These findings clearly show that modification of the phosphate surface of chrysotile fibres does not appear to alter the pleuropulmonary activities of the mineral, thus arguing against the earlier contention of less biological activity for chrysophosphate, a contention essentially based upon results of in vitro tests. This study strongly argues for in vivo testing of new fibrous materials before making definite conclusions about their biological activities.

Animals↗
PubMed1993

Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter.

This study was designed to determine whether beta-lactam antibiotics (cephalosporins and penicillins) are all substrates for the renal oligopeptide/H+ symporter and, if so, whether the transport system discriminates among the numerous beta-lactam antibiotics. We used [3H]glycylglutamine, [3H]cephalexin, and [3H]-ampicillin as probes for the transport of oligopeptides, cephalosporins, and penicillins in kidney brush border membrane vesicles, respectively. Among the beta-lactam antibiotics, only those with an alpha-amino group in the phenylacetamido moiety were found to interact with the oligopeptide/H+ symporter. Aminocephalosporins displayed high affinities (KiS generally < 250 microM), whereas aminopenicillins displayed low affinities (Ki 0.78-3.03 mM). These differences in affinities appeared to be a consequence of conformational features of the substrates, especially the sterical location of the carboxy group. The affinities of aminolactams for the oligopeptide/H+ symporter were, furthermore, related to the hydrophobicity of the phenylglycyl chains and the substituents attached to the thiazolidine and dihydrothiazine ring. In sharp contrast to the uptake of [3H]glycylglutamine and [3H]cephalexin, the uptake of [3H]ampicillin was not dependent on a pH gradient and was inhibited by various beta-lactam antibiotics, whether or not they contained an alpha-amino group. Our data suggest that: (a) the transport of aminocephalosporins is largely mediated by the oligopeptide/H+ symporter, which is highly influenced by the substrate structure; and (b) penicillins are transported by another system, which is less discriminative with respect to substrate structure.

Ampicillin↗