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Biomedical subjects

E Jover

Publications and source records attributed to E Jover.

35 records · Page 2Linked to original sources
PubMed1986

Activation of the voltage-sensitive sodium channel by a beta-scorpion toxin in rat brain nerve-ending particles.

Neurotoxins purified from scorpion venoms previously had been divided into two classes according to their binding properties in rat brain synaptosomes. However, the pharmacological action of beta-scorpion toxin (beta-ScTx) on this preparation has not yet been described. In this report we show that a beta-ScTx induced an increase in 22Na+ uptake through synaptosomal voltage-sensitive sodium channels since this stimulation was abolished by tetrodotoxin (TTX). The increase was smaller than with veratridine and no synergy was observed between beta-ScTx and veratridine, as is the case for alpha-scorpion toxin (alpha-ScTx) and veratridine. The effects of alpha- and beta-ScTx were additive and the concentration-effect curves for each type of toxin were not modified by the other, suggesting that these two types of toxins act through distinct and noninteracting receptor sites. This was confirmed by the absence of mutual modification of the equilibrium and kinetic binding properties. beta-ScTx was shown to inhibit the uptake and to stimulate the release of [3H]gamma-aminobutyric acid. These effects were blocked by TTX, and no synergy was observed with veratridine. It was concluded that all these effects are mediated by the activation of voltage-sensitive sodium channels induced by the binding of beta-ScTx to a receptor site (site 4) distinct from those for other neurotoxins acting on sodium channels.

Animals↗
PubMed1984

Binding of beta-scorpion toxin: a physicochemical study.

The binding to rat brain synaptosomes of a beta-scorpion toxin, i.e., toxin II of Centruroides suffusus suffusus (Css II), was studied as a function of pH, temperature, and concentration of some monovalent and divalent cations. At 10 degrees C and pH 6.0, the specific binding of 125I-labeled Css II corresponds to a single class of noninteracting high-affinity binding sites (KD = 0.18 nM) with a capacity (4.2 pmol/mg of protein) that is almost identical with that generally accepted for saxitoxin. The equilibrium dissociation constant of beta-scorpion toxin is pH independent, but the maximum binding capacity is reduced with increasing pH. Li+, guanidinium, Ca2+, Mg2+, and Mn2+ modified the apparent KD of the 125I-labeled Css II toxin. The equilibrium dissociation constant varies markedly with the temperature. The van't Hoff plot of the data is curvilinear, corresponding to a standard free-energy change associated with an entropy-driven process. The association rate constant also varies considerably with the temperature whereas the Arrhenius plot is linear between 1 and 30 degrees C. The energy of activation determined from these data is 17.6 kcal/mol. These results support the hypothesis that a cluster of nonpolar amino acid residues present on one face of the molecule is involved in the toxin-receptor interaction.

Animals↗
PubMed1984

Interaction of scorpion toxins with the sodium channel.

Scorpion toxins are miniproteins that have been characterized with regard to their molecular properties including their pharmacological action. On these bases, toxins specific to mammals or to insects have been described and within the first category alpha- and beta-toxins identified. These toxins were chemically modified and used as molecular probes of the sodium channel. Thus, the interaction of the toxins with the pharmacological target could be followed and a better definition of this target could be obtained.

Animals↗
PubMed1983

Photoaffinity labeling of alpha- and beta- scorpion toxin receptors associated with rat brain sodium channel.

Azido nitrophenylaminoacetyl [125I]iodo derivative of toxin II from Centruroides suffusus suffusus, a beta-toxin, and azido nitrophenylaminoacetyl [125I]iodo derivative of toxin V from Leiurus quinquestriatus quinquestriatus, an alpha-toxin, have been covalently linked after binding to their receptor sites that are related to the voltage sensitive sodium channel present in rat brain synaptosomes. Both derivatives labeled two polypeptides of 253000 +/- 20000 and 35000 +/- 2000 mol. wt. Labeling was blocked for each derivative by a large excess of the corresponding native toxin but no cross inhibition was obtained. These results suggest that both alpha - and beta - scorpion toxin receptors are located on or near the same two membrane polypeptides which may be part of the voltage dependent sodium channel.

Affinity Labels↗
PubMed1983

Alpha-scorpion neurotoxin derivatives suitable as potential markers of sodium channels. Preparation and characterization.

Modified scorpion neurotoxins, i.e. mono-biotinylated and mono-azido derivatives either on lysine 58 or lysine 60 have been characterized both at the structural level (sequence and circular dichroism) and by their pharmacological activity (toxicity to mice and ability to displace 125I-Androctonus australis Hector toxin II from its receptor sites. The results allowed us to pinpoint a region of the molecule including lysine residues 58 and 60 that is important for neurotoxin receptor interaction. Furthermore, as these derivatives retain, after 125I labeling, high binding capacities to synaptosomal membranes, they can be used as potential labels of the sodium channel either by covalent binding or using the avidin-biotin system.

Animals↗
PubMed1983

Glucagon and primary hyperlipidemias.

A reduction in glucagon secretion was found in a number of patients suffering from primary hyperlipidemias. This could be important in both the pathogenesis and classification of hyperlipidemias.

Glucagon↗
PubMed1982

Two types of scorpion receptor sites, one related to the activation, the other to the inactivation of the action potential sodium channel.

The action of the neurotoxin in Buthinae scorpion venoms (Androctonus, Buthus or Leiurus genera) has been extensively studied. These proteins induce a prolongation of the action potential of nerves and muscles by slowing down inactivation of the sodium channel. Their affinity for their receptor site depends on membrane potential. In the present report we describe a toxin from a Centrurinae scorpion, Centruroides suffusus, which binds rat brain synaptosomes at a receptor site distinct from the Buthinae scorpion site independently of voltage. We name Androctonus-like toxins, alpha-scorpion toxins (alpha-ScTX), and Centruroides-like toxins, beta-scorpion toxins (beta-ScTX). We further report that beta-ScTX induces repetitive firing in frog myelinated nerve fibres by producing an abnormal sodium permeability. The beta-toxin binds specifically to rat brain synaptosomes (Kd = 3 nM) and induces an inhibition of the uptake and a stimulation of the release of GABA at concentrations which are in good agreement with the Kd value. These effects are blocked by tetrodotoxin. The binding site of beta -ScTX is distinct from those of other neurotoxins acting on the sodium channel like tetrodotoxin, alpha-ScTX and veratridine. The alpha-ScTX/beta-ScTX binding site capacities decreases as development of rat brain synaptosomes progresses ; at day 7 after birth, it is 1.1. and at day 39, 0.3.

Action Potentials↗
PubMed1980

Comparative serum apolipoprotein studies in ischaemic heart disease and control subjects.

We have compared the concentrations of serum lipoprotein apoproteins in 55 ischaemic heart disease (IHD) patients and 116 apparently healthy control subjects by a simple, precise and reasonably sensitive "rocket" electroimmunoassay technique. Apolipoprotein B and apolipoprotein C levels in the vaery low density lipoprotein class and apolipoprotein B in the low density lipoprotein class were significantly lower IHD patients than in control subjects (p < 0.001). Apolipoprotein A levels within high density lipoproteins were markedly lower in a subpopulation of IHD patients compared with age-and sex-matched controls (p < 0.05). Using levels in excess of the 95th percentile of the levels in the healthy control population to delineate "abnormalities", we showed that there were more patients with "abnormalities" when lipoprotein apoprotein measurements were considered than when lipoprotein lipids were considered. The positive correlations between lipoprotein lipids and their apoproteins were in most instances greater in IHD patients than in controls.

Adult↗
PubMed1979

Effects of galactose, glucose and fructose on carbohydrate-lipid metabolism.

Doses of glucose, galactose and fructose were administered orally and intravenously, while monitoring the levels of blood glucose, serum insulin, free fatty acids, cholesterol and triglycerides. Blood glucose increases when glucose is administered orally or intravenously, but does not vary significantly with any other sugar. The increase in insulinemia only with oral and intravenous glucose and with oral galactose is in agreement with the participation of intestinal factors in the determination of insulin secretion. The results obtained for free fatty acids with the various sugars may be due to the metabolic properties of each sugar. We found no significant variations in the levels of cholesterol and triglycerides, perhaps because of the short duration of the experiment.

Administration, Oral↗
PubMed1977

Metabolic changes induced by human growth hormone.

In man purified human growth hormone shows anti-lipolytic effect and glycolysis is inhibited. The activity of lecithin-cholesterol-acyl-transferase is stimulated. The blood level of certain aminoacids fall.

Adult↗
PubMed1976

Purification of six neurotoxins from the venom of Dendroaspis viridis. Primary structure of two long toxins.

Six neurotoxins were purified from Dendroaspis viridis venom using gel filtration and equilibrium chromatography. The amino acid sequences of two of these neurotoxins (72 and 73 residues, five disulphide bridges) have been determined using almost exclusively automated Edman degradation. These two sequences are very similar: the only differences lies in the presence of one extra glycine at the C-terminal end of one of them. There is a good homology with the sequences of toxins now isolated from other Elapidae and Hydrophidae venoms.

Amino Acid Sequence↗
PubMed1976

Study of the effect of ACTH and cortisol on the plasms lipids in man using thin-layer chromatography.

This is a study of the action of ACTH and cortisol on plasma lipids using thin-layer chromatography and evaluation by densitometry. We have studied the action of 50 I.U. of ACTH in eight healthy individuals. We found an increase of free fatty acids after four hours and of triglycerides and esterified cholesterol after six hours. Free cholesterol levels declined after another six hours, the decrease becoming more intense after twenty-four hours. After twenty-four hours lecithin underwent a decline which is accompanied by an increase of lisolecithin. There was a decrease in the total amount of phospholipids. Seven patients received 100 mg. of cortisol intravenously over a period of ten minutes. We obtained an increase in free fatty acids after four hours and an increase of cholesterol after half and hour. We concluded that ACTH activates peripheral lipolysis thereby facilitating the hepatic synthesis of triglycerides and that it exerts a stimulating action on the lecithin-cholesterol-acyl-transferase system. Cortisol acts by facilitating the synthesis of triglycerides in the liver and increasing the hydrolysis of triglycerides in the plasma.

Adolescent↗