The serum apo E in rats following cholesterol diet and thymus treatment.
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Animals↗
Biomedical subjects
F Santangelo
Publications and source records attributed to F Santangelo.
[Afferents from a single muscle of the forelimbs and fastigial neurons of the cerebellum].
Responses of neurons in the medial nucleus of cerebellum (CBM) were studied on stimulation of ipsilateral and contralateral homonymous muscles, in decerebrated cats. The aim was to find out to what extent information from homonymous muscles of the forelimbs converge on the same CBM neurons and whether the probability of such a convergence depends on location (axial, proximal, distal) or function (flexor, extensor) of the tested muscles. The analysis was limited to the neurons belonging to the rostral part of the nucleus which is known to control the ipsilateral muscle periphery. Neuronal activity was recorded extracellularly using tungsten microelectrodes (5-12 M omega) and muscle stimulation was performed by bipolar coated steel electrodes, with the exception of the tip. At least 6 pairs of homonymous muscles were generally stimulated: two axial, two proximal and two distal in both forelimbs. Care was taken that, when a muscle was stimulated, the others were not activated either directly or in a reflex way. Out of the 65 neurons studied, 60 (92%) were responsive to muscle stimulation. It was specifically observed that a high percentage of cells reacted to stimulation of distal muscles (74% to ipsilateral and 71% to contralateral ones). More than half (55%) of the neurons were responsive to activation of a pair of homonymous distal muscles and about one third of them (31%) to both the pairs of distal muscles. On the contrary the percentage of responses to proximal muscles was reduced foremost in the ipsilateral ones (23%) and only an exiquous percentage of cells (15%) received information from the homonymous proximal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Afferent Pathways↗
Responses of cerebellar fastigial neurons to single muscle activation.
In lightly barbiturized cats, the discharges of neurons in the cerebellar fastigial nucleus (CBM) were recorded while single muscles in ipsilateral forelimb were activated by direct stimulation. The aim was to verify whether CBM cells could selectively detect the activity of afferent fibers from a muscle or a joint and to compare the various response characteristics of the rostral and the caudal division of the nucleus, which are known to control a different muscular periphery. Six muscles were routinely tested, two axial, two proximal and two distal ones. A good percentage of neurons in both partitions of the nucleus responded to the muscles tested (53% and 48% in the rostral and caudal part, respectively). In the rostral part of CBM a large proportion of cells (78% of those responsive) were influenced by one or more muscles having either the same function (the extensors or flexors) or acting on the same joint. Many such neurons showed a marked capability to respond to activation of distal muscles and a prevalence of inhibitory responses mainly on contraction of extensor and axial muscles. In the caudal division of the nucleus, 47% of the responsive cells displayed a stereotyped discharge pattern (excitatory or inhibitory) in response to activation of any tested muscle. In contrast to the rostral CBM the incidence of responses to proximal and distal muscles was about equal in the caudal CBM and a majority of neurons had excitatory responses to flexor muscle contraction. The latencies of the excitatory effects ranged from 8 to 53 ms in rostral and 9 up to 69 ms in caudal CBM.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Bicyclic compounds with potential antiulcer and/or antisecretory activity. I. 4,5,6,7-Tetrahydrobenzimidazoles.
The remarkable antiulcer and antisecretory activity of some previously described 4,5,6,7-tetrahydroimidazo[4,5-c]pyridine derivatives prompted us to further investigate related bicyclic systems. Accordingly, a series of 5-amino- and 5-aminomethyl-4,5,6,7-tetrahydrobenzimidazoles, regiospecifically alkylated in position 1, were synthesized and tested. Only a few 1-ethyl-5-amino derivatives displayed a reasonable antiulcer activity in comparison with our former class of compounds.
Animals↗
[Thymus-hypophysis-thyroid interrelation in rats after administration of a heterologous extract of thymus gland].
The Authors have investigated the effects of a thymus chromatographic fraction on TSH, T3, T4 serum values in thyroidectomized and normal controls rats before and after thymus treatment. The decrease in TSH values of thyroidectomized rats points out a possible inhibitory effect which the thymus extract may have at either the level of the adenohypophysis or hypothalamus. Moreover the TSH values in the euthyroid rats after thymus treatment showed a slight decrease, this changes are much more evident in the thyroidectomized rats after thymus treatment. In fact the plasma TSH of thyroidectomized rats drops from 97.5 +/- 4 microU/ml before thymus treatment, to 76.25 +/- 10 microU/ml after thymus treatment.
Animals↗
Comparative study of GABA-mediated depolarizations of lumbar A delta and C primary afferent neurones of the rat.
The distribution of GABA receptors on various categories of primary afferents was studied by means of intracellular recordings from rat dorsal root ganglion neurones. Cells were identified on the basis of their conduction velocity and classified as A delta and C neurones. Transient applications of GABA led to a decrease of membrane resistance and a concomitant depolarization. Maximal GABA-induced responses were weaker in C than in A delta and A beta cells. Smaller conductance changes in C cells suggest a lower density of GABAA receptors, and the heterogeneity of the "membrane potential/response amplitude" relationship indicate that the ionic mechanisms underlying GABA-induced responses may not be uniform on all primary afferents; this is supported by the wide range of reversal potential values recorded under voltage-clamp conditions in A delta cells.
Afferent Pathways↗
Coexistence of GABAA and GABAB receptors on A delta and C primary afferents.
Intracellular recordings from adult rat dorsal root ganglion neurones were performed in vitro and the coexistence of two gamma-aminobutyric acid (GABA) receptors on the membrane of identified A delta and C primary afferents was demonstrated. Transient applications of GABA (10(-6)-10(-2) M) evoked dose-dependent depolarizations and increased membrane conductance. The responses were mimicked by muscimol, isoguvacine, THIP and 3 amino propane sulphonic acid (3 APS); they were blocked by bicuculline and picrotoxin. Pentobarbitone induced an increase of GABA-induced depolarizations. Perfusion of tetraethylammonium (TEA, 7.5 mM) and intracellular injection of Cs+ ions unmasked the Ca2+ component of action potentials, which appeared as long-lasting plateau depolarizations. Such action potentials were shortened in the presence of methoxyverapamil (D600, 5 X 10(-6)-10(-5) M) and in a medium without Ca+ ions. Prolonged (5-10 min) perfusion of GABA (10(-9)-10(-5) M) shortened the Ca2+ component of action potentials. This effect was mimicked by baclofen (10(-7)-5 X 10(-6) M) and muscimol (5 X 10(-7)-10(-5) M) and was not affected by bicuculline perfusion (5 X 10(-6)-10(-5) M). Isoguvacine (2.5 X 10(-5) M) did not affect action potential duration. It is concluded that two GABA receptors coexist on the membrane of slow conducting primary afferents: the bicuculline-sensitive GABAA receptor mediates depolarizations and the bicuculline-insensitive GABAB receptor shortens the calcium component of action potentials.
Action Potentials↗
[Comparative analysis of the facilitating effects induced on muscular periphery by the microstimulation of various cerebellar nuclei].
The facilitatory effects evoked on the motor periphery by the activation of neuronal pools in cerebellar nuclei were analized in 13 cats. The aim of the work was to compare the frequency and the characteristics of the motor facilitations induced on the ipsilateral forelimb by the microstimulation of cerebellar foci in the fastigial (CBM or in the interposital (NIA) nucleus. CBM or NIA sites, previously identified for the motor effects, were microstimulated, together with the contralateral motor cortex, to give evidence of the facilitations. It was observed that 51% of the NIA motor sites, 46% of the rostral and 33% of the caudal CBM ones, were able, when activated, to evoke facilitatory effects on at least one muscle. The most frequent motor pattern observed following NIA microstimulation was the contraction of a proximal muscle and simultaneously the facilitation of a distal one. Similar responses were detected upon activation of neuronal pools in both zones of CBM. A good number of CBM foci (39% in the rostral division and 33% in the caudal one), however, was unable to induce facilitation, eliciting, upon stimulation, only massive axial movements. Distal muscles were involved by facilitatory effects in a higher number of cases following NIA stimulation (61% of all the facilitatory responses) than CBM rostral (39%) or caudal (43%) one. Furthermore, a particular characteristic of a good percentage of CBM facilitating foci (36% in rostral and 28% in caudal CBM) was the capability to elicit motor activity in the contralateral side and simultaneously facilitation in the ipsilateral one.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of a thymus fraction on the haematic ApoB of rats fed on a diet rich in cholesterol.
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Animals↗
Solid-phase synthesis of sauvagine-(17-40).
The solid-phase synthesis of the tetracosapeptide corresponding to the C-terminal amino acid sequence of sauvagine is described. After purification by gel filtration, the polypeptide appeared to possess an acceptable degree of homogeneity, as judged by different kinds of electrophoresis and chromatography, and by automated Edman degradation analysis. Preliminary pharmacological results indicate that the fragment-(17-40) is practically devoid of any sauvagine activity on the circulatory system and endocrine glands; a weak effect on gastric emptying delay has been demonstrated (1% of the natural product).
Amino Acid Sequence↗
Electrophysiological study of GABAA versus GABAB receptors on excitation-secretion coupling.
Inwardly-directed Ca++-currents are caused by numerous types of action potentials which would not otherwise cause secretion. This process is regulated electrically and by neurotransmitters. We have studied in vitro the ionic mechanisms of GABA-mediated presynaptic inhibition and thereby the distinctive characteristics of GABAA and GABAB receptors: i.e., the GABAA system, which produces such short-lasting changes that there is an instantaneous reduction of spike amplitudes, in particular by opening Cl- -conductance, and the GABAB system, which results directly in inhibition of secretion due to a tonic depression of Ca++-currents. The principal aim was to determine if GABAB/Ca++ receptors could coexist on a membrane already possessing a large number of GABAA/Cl- sites available for presynaptic inhibition. Intracellular recordings of A delta and C dorsal root ganglion cell bodies were used as a model for the study of preterminal axonal membranes. Results were tentatively correlated with those obtained extracellularly by recording Ca++ and K+ movements (Cl- being assessed indirectly) from a set of other cells which also secrete neuropeptides by exocytosis: e.g., endings of unmyelinated fibres in the neurohypophysis and clusters of innervated gland cells in the pars intermedia. In recent years there has been a growing interest in receptors for neurotransmitters (e.g., monoamines, peptides, gamma-aminobutyric acid) modulating Ca++-dependent secretion in various biological systems (14-16, 24, 25, 29, 34). Modulation is possible either by changing the basic characteristics of the ionic currents during a standard action potential (Na+/K+ voltage transients being markedly altered by repolarizing K+ currents) or by any kind of direct action on voltage-dependent Ca++-channels: the latter will allow Ca++ to enter the cell in graded amounts not only as parts of well-defined Ca++-spikes (16, 14, 39; see also 24, 26, 28) but of well-defined Ca++-spikes (16, 14, 39; see also 24, 26, 28) but possibly also along complex sequences of tail-currents (for the biophysics, see 28, 29). Accordingly, it is essential to study presynaptic actions of transmitters in systems where spikes can be recorded, though presynaptic receptor activation can sometimes be identified by other means than spiking patterns (e.g., membrane effects in relation to other well-defined ionophores). The study of cells which are in contact with synapses synthesizing and releasing gamma-aminobutyric acid (GABA) has drawn much of the attention given to these problems.(ABSTRACT TRUNCATED AT 400 WORDS)
Afferent Pathways↗
The role of the thyroid hormones on the decrease of cholesterolemia produced by a thymus fraction.
The purpose of this paper is to establish whether the hypocholesterolemic effect of thymus fraction administered to rats fed on a fat diet is correlated to an activation of thyroid. By determining the plasma levels of T3,T4 by kit set/RIA and TSH by the method of Jaquet et al., modified for rats, the authors may exclude this hypothesis confirming the results of Comsa et al, of an inhibitory effect of thymus in TSH secretion.
Animals↗
[Effects of 2 thymus extracts on blood levels of cholesterol and glucose in the rat].
The effects of two calf thymus extracts (fraction III and Tp1) on the haematic levels of cholesterol and glucose in the rat on a fat diet have been compared. The fraction III carries out a very marked decrease of cholesterolemia without changes in the levels of glycemia. On the contrary the Tp1 determines only a moderate decrease of cholesterolemia but a very marked decrease of glycemia. Thherefore these results seem both to confirm the differences between the two thymus extracts and the metabolic actions of thymus.
Animals↗
Direct action of pentobarbitone in potentiating the responses to GABA of rat dorsal root ganglion neurones in vitro.
Pentobarbitone (PB) was tested for effects on responses to GABA recorded intracellularly in rat dorsal root ganglion neurones. Concentrations of over 1 mM PB elicited small depolarizations, whereas at greater than or equal to 10 microM PB readily potentiated depolarizations and increased membrane conductance evoked by GABA. The GABA antagonists bicuculline and picrotoxin reduced PB-potentiated and equiamplitude control responses to the same degree. Since an action of PB on GABA transport is unlikely in this tissue, the PB effects probably occur at the receptor-ionophore complex.
Action Potentials↗
Influences of precerebellar systems triggering movement on single cells of the interpositus nucleus of the cat.
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Afferent Pathways↗
Synthetic peptides related to the dermorphins. I. Synthesis and biological activities of the shorter homologues and of analogues of the heptapeptides.
Dermorphins are potent opiate-like peptides isolated from the skin of some species of frogs. They are characterized by the presence of a D-amino acid residue, which is crucial for bioactivity. A number of analogues were prepared in order to evaluate the structure-activity relationships. The syntheses were accomplished either by conventional or solid-phase procedures. In vitro assays included both guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Central analgesic (tail-flick and hot plate tests) and cataleptic activities were determined in the rat by intracerebroventricular route. The potency of dermorphin (H- Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) in the different tests was: GPI: IC50 = 3.3 nM; MVD: IC50 = 29 nM; hot plate: ED50 = 13.3 pmol/rat; tail-flick: ED50 = 23 pmol/rat; catalepsy: ED50 = 130 pmol/rat.
Analgesics↗
SL 75 102 as a gama-aminobutyric acid agonist: experiments on dorsal root ganglion neurones in vitro.
1 In anticipation that centrally active gamma-aminobutyric acid (GABA)-mimetic drugs may be clinically useful, derivatives of GABA with an imine link (Schiff base) to a lipophilic carrier have recently been prepared. The present paper concerns the actions of [alpha(4-chlorophenyl)5-fluoro, 2-hydroxy benzilidene-amino]-4-butanoate Na+, SL 75 102. 2 To test one aspect of the GABA-mimetic properties of SL 75 102, this compound was compared with GABA for activity on intracellularly-recorded neurones in rat dorsal root ganglia in vitro. On these neurones GABA, administered either by microiontophoresis or direct into the superfusion medium, causes a depolarization, due to an increased chloride conductance, followed by a period of desensitization. 3 The actions of Sl 75 102 were in nearly all respects identical to those of GABA; parameters examined were the effects on membrane potential and input conductance, desensitization, dose-response characteristics and sensitivity to the GABA antagonists, bicuculline and picrotoxin. 4 SL 75 102 was less potent than GABA (mean relative potency 0.03:1). 5 SL 75 102 therefore appears to be a weak agonist at GABA receptors of these neurones.
Animals↗
Physiological study of amino acid uptake and receptor desensitization: the GABA system in dorsal root ganglia.
GABA applied under microscopic vision (x320) to neurones of isolated DRG, triggers a depolarizing outflow of Cl-, as seen in intracellular recordings of large somata with myelinated fibres. Group C neurones have now also been examined with respect to diversity of GABA receptors. Cells of small diametre (less than 30 micrometers) responding to stimulation of slow conducting, (less than 2.5 m/sec) unmyelinated C fibres were studied for 2 reasons: 1) GABA probably depolarizes nerve endings and C fibres but conductance changes have not been determined, 2) the inference that, unlike group A, the group C neurones show an additional response to GABA by reducing the net influx of Ca++ during action potentials. As a first step in comparing group A with C neurones, it was found that all ganglion cells responded similarly to GABA with Cl--dependent depolarization and a rapid desensitization. This conclusion relies on combined physiological and pharmacological data and also on autoradiographs of glial GABA uptake. Results are considered to reflect direct actions of GABA on neuronal membranes and to be independent of secondary effects due to Na+-dependent transport of GABA into glia.
Amino Acids↗