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P A Ferchmin

Publications and source records attributed to P A Ferchmin.

At least 19 recordsLinked to original sources
PubMed1995

Spermine increases paired-pulse facilitation in area CA1 of hippocampus in a calcium-dependent manner.

The effect of spermine on neurotransmission was studied in area CA1 of the hippocampal slice preparation. Paired-pulse stimulation (20 ms interpulse interval) was delivered to stratum radiatum; the evoked field potential responses were recorded simultaneously from stratum radiatum and from stratum pyramidale. At mM and sub-mM concentrations, spermine decreased the slope of pEPSP in stratum radiatum and the area of the conditioning population spike in stratum pyramidale. Short-latency paired-pulse inhibition of the population spike was converted to facilitation by spermine. These effects of spermine resembled those observed at low calcium concentration. In addition, dose-response and input-output curves determined at various Ca2+ concentrations demonstrated that the depressant effects of spermine were larger at low Ca2+ levels. The results support the notion that spermine competitively blocks presynaptic voltage-sensitive Ca2+ channels, thus causing a decreased release of neurotransmitter. Since spermine is present in brain, it is likely that it is a natural modulator of Ca2+ channels.

Animals↗
PubMed1994

Spermine depresses NMDA, K/AMPA and GABAA-mediated synaptic transmission in the rat hippocampal slice preparation.

The effects of spermine, an endogenous polyamine, were examined in area CA1 of the rat hippocampal slice preparation. Spermine, at low millimolar concentrations, rapidly and potently depressed NMDA and K/AMPA-mediated population EPSPs, and GABA-mediated monosynaptic population IPSPs. These effects contrast with its well-known potentiation of NMDA currents at lower concentrations. Our results raise the possibility that the large intracellular stores of spermine that are released after various neural insults could act as an endogenous neuroprotective mechanism by limiting excessive calcium entry.

Animals↗
PubMed1994

Metabolic activation of the brain of young rats after exposure to environmental complexity.

Autoradiography with 14C-2-deoxyglucose was used to determine brain metabolic activity during the quiet period that follows after daily exploratory experiences in new complex environments. Eight 1-month-old, male Tryon rats were selected from two litters. Pairs of littermates matched by body weight were assigned to one of two conditions: rats housed individually in small home cages as the "impoverished condition," or rats exposed twice daily to changing and complex environments of two large cages with inanimate objects and conspecifics as the "enriched condition." After 4 days, rats were injected with 2-deoxyglucose, placed individually in a home cage and left undisturbed for 90 min until sacrificed. The brains of "enriched" rats were heavier than their "impoverished" littermates, and showed a global trend for metabolic enhancement. They also showed significantly greater amounts of 2-deoxyglucose in occipital cortex (27%), hippocampal subiculum (36%), and nucleus accumbens (40%).

Aging↗
PubMed1993

alpha-Difluoromethylornithine decreases inhibitory transmission in hippocampal slices independently of its inhibitory effect on ornithine decarboxylase.

We tested the effect of DL-alpha-(difluoromethyl)ornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC), on recordings in area CA1 of rat hippocampal slices. In the concentration range in which it is used as an ODC inhibitor, DFMO increased neuronal excitability and blocked paired-pulse inhibition. The effect of DFMO was reversed by perfusing the slice with normal bathing solution. These effects were not attenuated by the simultaneous addition of putrescine; thus the activity of DFMO was not related to a decrease in putrescine caused by the inhibition of ODC. Mediation by the N-methyl-D-aspartate (NMDA) receptor was ruled out because DL-2-amino-5-phosphonovalerate (APV), an NMDA antagonist, did not block the effect of DFMO. Intracellular and extracellular recordings of pharmacologically isolated IPSPs supported the notion that DFMO depressed GABAergic transmission. DFMO has frequently been used as a tool to study the role of the ODC-polyamine system in neural preparations. This report suggests that the results from such studies must be interpreted with caution. In addition, our findings raise questions about the proposed use of DFMO as a neuroprotective agent against excitotoxicity.

2-Amino-5-phosphonovalerate↗
PubMed1993

Diterpenoids from Caribbean gorgonians act as noncompetitive inhibitors of the nicotinic acetylcholine receptor.

1. Three cyclic diterpenoids isolated from gorgonians of the Eunicea genus and characterized as eupalmerin acetate (EUAC), 12,13-bisepieupalmerin (BEEP), and eunicin (EUNI) were found to be pharmacologically active on the nicotinic acetylcholine receptor (AChR). 2. The receptor from the BC3H-1 muscle cell line was expressed in Xenopus laevis oocytes and studied with a two-electrode voltage clamp apparatus. 3. All three compounds reversibly inhibited ACh-induced currents, with IC50's from 6 to 35 microM. ACh dose-response curves suggested that his inhibition was noncompetitive. The cembranoids also increased the rate of receptor desensitization. 4. Radioligand-binding studies using AChR-rich membranes from Torpedo electric organ indicated that all three cembranoids inhibited high-affinity [3H]phencyclidine binding, with IC50's of 0.8, 11.6, and 63.8 microM for EUNI, EUAC, and BEEP, respectively. The cembranoids at a 100 microM concentration did not inhibit [alpha-125I]bungarotoxin binding to either membrane-bound or solubilized AChR. 5. It is concluded that these compounds act as noncompetitive inhibitors of peripheral AChR.

Animals↗
PubMed1992

Electric organ polyamines and their effects on the acetylcholine receptor.

1. The electric organ of Torpedo nobiliana contained putrescine (PUT), spermidine (SPD), spermine (SPM), and cadaverine (CAD). Traces of acetylated SPD and SPM were occasionaly seen. 2. Upon fractionation of the tissue by differential centrifugation, the polyamines (PA) were found predominantly in the soluble fraction. The postsynaptic membrane fraction, containing a high concentration of acetylcholine receptor (AChR), was proportionally enriched in SPM. The molar ratio of SPM to AChR was approximately two in these membranes. 3. The effect of exogeneous PA on AChR function was studied by two methods: carbamoylcholine (CCh)-dependent 86Rb+ influx into receptor-rich membrane vesicles and [alpha-125I]bungarotoxin (Bgt) binding to the AChR. 4. SPM inhibited both ion influx and the rate of Bgt binding at concentrations above 1 mM, and therefore it appears to act as a competitive antagonist of the AChR. 5. At submicromolar concentrations, and only after preincubation with the receptor-rich membrane, SPM and PUT increased the ion influx by about 20% over control values. 6. Preincubation with 100 nM SPM did not affect the equilibrium binding of iodinated toxin or the rate of toxin binding, and therefore SPM was not uncovering new receptors. 7. By measuring the initial rate of toxin binding after different periods of preincubation with 1 microM CCh, the rate of the slow phase of receptor desensitization was determined. This rate was not changed by 100 nM SPM. 8. Although these results suggest that at low concentrations SPM is a positive modulator of the AChR, the precise mechanism of action is not determined yet.

Animals↗
PubMed1990

Putrescine decreases exploration of a black and white maze.

The effect of putrescine and cyclohexylamine on rat cortical polyamine concentration and on behavior in a black and white maze was studied. The levels of polyamines in brain cortex were determined 15 min, 2, 4, and 6 hours after injection of putrescine (200 or 400 mg/kg) or cyclohexylamine (380 mg/kg). Putrescine concentration increased 6-fold 15 min after injection of putrescine followed by a decline during the next 6 hours. Cyclohexylamine increased putrescine concentration doubling it 4 hours after injection. Spermidine and spermine concentrations did not change after either putrescine or cyclohexylamine injection. Behavior was studied in the Greek cross maze which provides the choice to enter either white or black compartments. Putrescine 200 mg/kg decreased entries into white but not black compartments, while putrescine 400 mg/kg decreased entries into both. The effect of cyclohexylamine was similar to putrescine 400 mg/kg. The behavioral effect of each treatment was independent of the time between injection and testing for up to 6 hours, while the levels of putrescine changed during the same period. Therefore, behavior was not directly related to total cortical putrescine.

Animals↗
PubMed1990

Experience affects cortical but not subcortical polyamines.

The effect of brief periods of experience in an enriched environment (7 hours per day for 3 days), and of inhibition of polyamine synthesis was studied in four brain regions: occipital cortex, remaining cortex, subcortex and cerebellum plus medulla. Polyamine synthesis was inhibited by alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. DFMO caused a 30-50% decrease in putrescine content in all brain areas, irrespective of the environmental treatment. Spermidine was decreased by the inhibitor in subcortex and in cerebellum plus medulla, while spermine was increased in remaining cortex. The regional differences in inhibitor effect suggest that the regulation of polyamine metabolism varies among the four brain areas. Experience increased the weight and spermidine content of remaining cortex and decreased putrescine content of occipital cortex. Noncortical areas were not affected. The effects of experience on polyamine levels were somewhat increased by DFMO. Therefore, experience did not have a generalized effect on polyamine levels; rather, each polyamine responded in a specific manner. In addition, polyamine levels were affected only in those brain areas which are known from previous studies to respond to environmental stimulation with weight increase. These facts suggest that polyamines might have a role in the regulation of experience-induced plasticity.

Animals↗
PubMed1989

Positive modulators of muscle acetylcholine receptor.

A solution of succinic anhydride (SA) in buffer N-tris(hydroxymethyl)methyl-2-aminoethane sulfonic acid (TES), the SATES solution, potentiates the effect of carbonyl containing agonists on frog muscle (del Castillo et al., Br. J. Pharmac. 84: 275-288, 1985). Here we report that the main compound in the SATES solution is a monosuccinyl ester of TES (MST). This compound is not an agonist of the acetylcholine (ACh) receptor nor is it an inhibitor of ACh esterase, yet MST potentiates the ACh-induced tension and depolarization in frog muscle to a new maximum. It increases the amplitude of miniature endplate potentials but has no effect on the time course of miniature endplate currents. The acetylated analogue of MST (mono-acetyl-TES: MAT) had similar but more pronounced effects on frog muscle. Neither MST nor MAT affect [3H]Ach binding to receptor-rich membranes from the electric organ of Torpedo californica, or the affinity state transition induced by agonists. Radiolabeled MST does not bind to these membranes and MAT does not alter agonist-induced ion flux. Therefore, these compounds seem to act as positive modulators of muscle ACh receptor but are inactive in Torpedo vesicles.

Acetylcholine↗
PubMed1987

Role of polyamines in experience-dependent brain plasticity.

Enriched experience increases brain growth, neuronal differentiation and learning abilities. Polyamines are modulators of growth and differentiation. We studied the effect of difluoromethylornithine (DFMO, an inhibitor of putrescine synthesis) on brain growth of rats exposed either to a complex or an impoverished environment. In both environmental conditions, DFMO decreased cortical putrescine by 50% and increased spermine by 13%; spermidine remained constant. Cortical RNA was not affected significantly by DFMO but DNA was decreased exclusively in rats exposed to the impoverished environment. Environmental complexity increased cortical weight, RNA and spermidine content. These differences were larger in DFMO-injected rats than in saline controls. Since stimulants such as amphetamines also enhance the environmental effects it was conceivable that DFMO might act as a stimulant. We have measured the effect of DFMO on rats' exploratory activity and found it decreased by the drug. Therefore the enhancing effect of DFMO cannot be explained by its behavioral activity. We propose that DFMO enhances the experience-dependent brain plasticity by facilitating differentiation of neurons.

Animals↗
PubMed1986

Forty minutes of experience increase the weight and RNA content of cerebral cortex in periadolescent rats.

The goal of this work was to determine the shortest period of exposure to environmental complexity (EC) that would produce measurable changes in brain weight or RNA content. This period varied with the age of subjects. In young adult rats, 3 months old, 4 days of exposure to EC increased the RNA concentration in the occipital cortex above the level of littermates kept in impoverished condition (IC). Cortical weight was not affected. Seven or one daily hrs of exposure to EC did not produce significant differences between rats in EC and IC. In periadolescent rats, 30- to 40-day-old, 1 daily hr of enrichment for 4 days increased both the weight of occipital cortex and its RNA content. Exposures of 7 or 24 hrs/day produced similar results. In another experiment with periadolescent rats 1 hr or even 10 min of exposure to EC per day, for 4 days, increased total cortical weight and RNA content. Thus, periadolescent rat brain display remarkably high plasticity. These very short exposure periods are comparable to the duration of learning sessions in simple formal trainings.

Animals↗
PubMed1985

Succinyl derivatives of N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid: their effects on the frog neuromuscular junction.

Succinic anhydride (SA) dissolved in Ringer solution buffered with N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid (SA-TES solution) potentiates the depolarizing action of acetylcholine (ACh, 10-40 microM) on frog muscle and the tension induced by bath application of this agonist. Applied from one side of a double-barrelled micropipette, SA-TES increases the amplitude of iontophoretically elicited ACh potentials. The potentiation of the effects of ACh by SA-TES does not involve changes in either the activity of the ACh esterase or the input resistance of the muscle membrane. For depolarizations of frog sartorius muscle, dose-response relationships obtained for ACh concentrations from 0.5 to 20 microM indicate that SA-TES increases the apparent affinity of ACh by a factor of 3. SA-TES exerts an "accelerating' effect on the responses elicited by bath-applied ACh; i.e., it increases the rate of depolarization when ACh is added to the bath and the rate of repolarization upon washing out. These effects are particularly marked in preparations treated with neostigmine (3 microM). SA-TES does not potentiate the depolarizing action of agonists which do not contain an ester group. Moreover, the time course of the responses elicited by these compounds is not influenced by SA-TES. SA-TES fails to influence significantly the effects of the neurally released transmitter. Only a 10% increase in the average amplitude of the endplate potentials was observed. SA hydrolyzes in about 30 min at room temperature; however the SA-TES solution retains its activity for several weeks. Succinate is inactive, and so is SA in Ringer buffered with phosphate. The SA-TES solution contains seven succinyl-TES derivatives, which were separated by ion-exchange chromatography and paper chromatography. At concentrations between 1 to 150 microM, these succinyl-TES derivatives affected the ACh-induced contraction of frog rectus abdominus muscle. The most abundant derivative potentiated the action of high doses of ACh, but was inhibitory at lower ones. The other derivatives were mostly inhibitory. These results are discussed in terms of two hypotheses. One postulates the presence of a diffusion barrier formed by groups that bind ACh and are saturated by SA-TES. The other assumes that SA-TES acts directly on the ACh receptor exerting its potentiating effect through a cooperative mechanism.

Acetylcholine↗
PubMed1985

Interaction with objects by group-living Saimiri sciureus.

We have studied the spontaneous interaction with small, inedible objects by group-living Saimiri. Twenty-one animals living in a large outdoor enclosure were presented with a set of 10 novel objects of diverse materials, colors, sizes, and shapes. We have used a sampling technique to record the number of monkeys interacting with each object; qualitative observations complemented these measurements. Next day the same objects were presented again and the observations continued. This experiment was repeated with some variations three times over a period of six months. The highest score for novel objects was obtained immediately upon objects presentation; afterwards the score sharply decreased for that day. On second presentation of the same objects the scores were more evenly distributed during the day, the cumulative total resembling that of day one. Objects' characteristics influenced the amount of interaction with them. The important factors seemed to be the material the objects were made of and their complexity. The objects that were contacted most frequently elicited intense investigative behavior and social play. These results differ from some previous works in which Saimiri were observed to interact only rarely with novel objects.

Animals↗
PubMed1977

Predicted secondary structure of snake venom toxins from their primary structures.

We have predicted the secondary structure of 38 snake venom toxins using the method of Chou and Fasman. Our predictions indicate that beta-chain and random coil structures predominate in these proteins. The conformations of long neurotoxins, short neurotoxins and cytotoxins are less similar than previously believed. Cytotoxins contain 40--50% of beta-structure and they form a notably homogeneous group. Short neurotoxins contain less beta-structure (13--30%) and more random coil than cytotoxins, and they also form a more heterogeneous group in terms of secondary structure. The characteristics of long neurotoxins are intermediate to the above mentioned groups. Experimental evidence supporting these propositions is discussed.

Amino Acid Sequence↗