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Biomedical subjects

L Re

Publications and source records attributed to L Re.

At least 37 records · Page 2Linked to original sources

[Persistence of the control of the fluctuations of heart rate in the anesthetized and pithed adult rat. Effect of enteraminergic drugs].

Spontaneous fluctuations in heart rate were analyzed by spectral analysis in the ether anesthetized and pithed adult rat. In order to investigate the changes in the spectral pattern of the fluctuations, the selective 5HT-2 and -3 isoreceptor blockers ritanserin and BRL 43694A were used. In both the experimental conditions, ritanserin blockade led to dose-dependent increased fluctuations in HR low and high frequencies. In both the anesthetized and pithed rats, the low frequency range HR fluctuations were drastically reduced by BRL 43694A.

Anesthesia↗

Sodium-activated potassium current in mouse diaphragm.

The mouse diaphragm muscle fiber was studied using the loose patch clamp technique. The voltage gated sodium currents were evoked by step pulses from a holding potential of about - 70 mV. Following the activation of the sodium current, a very large and fast outward current was evoked. The sensitivity of this current to 4-aminopyridine and tetraethylammonium indicates the potassium ion as the possible carrier for the channel. Furthermore, the sensitivity to tetrodotoxin and extracellular sodium demonstrated the sodium dependence of this current.

Action Potentials↗

Characterization of the rabbit aorta endothelium-dependent cholinergic receptor by agonist equipotent molar doses.

The endothelium-dependent acetylcholine, metacholine, carbachol, betanechol, and furtrethonium relaxation values have been measured in vitro for the rabbit aorta, in presence of a high concentration of hexamethonium. The produced EPMR values complete the values that were obtained in a previous experiment under analogous conditions for rat bladder, ileum, iris, stomach, and trachea preparations. The complete set was analyzed by new statistical techniques of data analysis and display, which are both simpler and more precise than the statistical modeling techniques used by us in the past. This has led to new results concerning the clustering of drugs and of receptors, as well as to a characterization of the endothelium receptor.

Animals↗

Computerized estimation of spontaneous and evoked acetylcholine release at the neuromuscular junction.

A new and automated on-line analysis of the parameters related to the neuromuscular activity is shown. The procedure used to obtain in real time the statistical evaluation of the recorded electrical signals is presented and discussed. The hardware is composed of a PDP-11/73 microcomputer equipped with an analog input/output board. The software is written principally in FORTRAN 77 and also uses MACRO/ASSEMBLY language.

Acetylcholine↗

Effects of famotidine at the mouse neuromuscular junction compared with those of cimetidine and ranitidine.

The effects of some histamine H2-receptor antagonists on the cholinergic system have been evaluated at the mouse end-plate. Previous data revealed interactions at both pre- and postsynaptic sites for cimetidine and ranitidine. The present work shows the effects of the same two drugs, and of famotidine, on some parameters related to the neuromuscular transmission. Ranitidine potentiates the amplitude of the spontaneously occurring miniature end-plate potentials. Famotidine reduces the same parameter. A common effect achieved with higher concentrations of the three drugs is the reduction of the quantal content. The kinetic parameters of the quantal conductance change is lengthened, in a different manner, by all the assayed drugs too. These results, besides strengthening the hypothesis of an inhibitory action of ranitidine on acetylcholinesterase, indicate a collateral inhibitory effect at presynaptic levels of cimetidine, ranitidine and famotidine.

Animals↗

Variation in thin filament size in the skeletal muscle of the frog.

The sartorius muscle of Rana esculenta was fixed and dehydrated by different methods and cross-sections of sarcomeres of different lengths were examined by electron microscopy. The area within the outlines of the thin filaments in negatives was measured using a high-resolution television system and a graphics tablet or by using a microdensitometer and computer processing the images with a density threshold above the background level. In all specimens the area of the thin filaments in the I-bands was found to be larger than in the S-zones of the A-bands where the thick and thin filaments interpenetrate. The difference was statistically significant and independent of the length of the sarcomere. The results are in agreement with previous observations in glycerol-extracted fibres. It is suggested that the change in size of the thin filaments might be accounted for by some interaction with the thick filaments.

Actin Cytoskeleton↗

A further study on the kinetics of the subcellular current events at the mouse end-plate in the presence of cimetidine and ranitidine.

The cholinomimetic activity of Cimetidine and Ranitidine has been demonstrated by several authors. In the aim to better understand the phenomenon, we analyse the miniature end-plate current decay time. The prolongation of the decay phase of the synaptic current induced by the "selective" H2-antagonist Ranitidine, and to a lesser extent and at higher concentrations by Cimetidine, resembles that of the cholinesterase inhibitors. These agents usually prolong the quantal conductance change having little or no effect on the channel lifetime. The results of our previous experiments, which data were obtained by analyzing the "voltage" events, either spontaneous or evoked, of a classic frog preparation, showed a marked alteration of the temporal parameters. These effects, obtained at higher drug concentrations than those used in the present work, are now better defined by deriving extracellularly the "current" events. The results are also compared with those obtained by assaying the cholinesterase inhibitor Eserine, under the same experimental conditions.

Animals↗

The usefulness, in pharmacological classification, of complementary pattern-recognition techniques and structure modelling as afforded by the iterative collation of multiple-trial data in data banks.

In this emerging information age no significant limits can be envisaged to the immense resources of knowledge that pharmacological sciences can draw upon by systematically applying multivariate pattern-recognition techniques to those data banks which can be organized internationally with better standardization of descriptors, i.e. by parametrizing observations and evaluating monitoring in experimental, biological assays, clinical trials and postmarketing surveillance. Even conventionally or habitually adopted references and communalities such as traditional drug profiles and receptor models may be iteratively re-checked and suitably adapted so as to take account of more adequate, up-to-date analytical techniques, fresh biological ideas and new advances in terms of physiological refinements. An attempt may also be made to modify the chemicophysical relationships and patterns currently traced on the basis of what are held to be quantitative structure-activity oversimplifications. The present paper focuses upon specifying a number of standardization criteria in conventional assays and upon submitting multiple biological features to monitoring; in addition, it gives some picture of the new trends the approach can offer and draws attention to the more relevant, innovative literature references.

Animals↗

Electrophysiological analysis of the cholinergic effects of cimetidine and ranitidine.

The study takes the form of an analysis of the effects of cimetidine and ranitidine (2 x 10(-4) M) on 9 electrophysiological parameters, using a single frog sciatic nerve-sartorius muscle preparation. The parameters evaluated were: (i) mean end-plate potential (e.p.p.) amplitude, and mean 50%-corrected e.p.p. amplitude, (ii) mean rise time (RT), (iii) mean half-decay (HD), (iv) mean miniature end-plate potential (m.e.p.p.) amplitude, (v) mean resting membrane potential (RMP), (vi) mean m.e.p.p. frequency (f), (vii) mean quantal content (m), (viii) quantum release probability (p), and (ix) number of active sites (n) in the nerve terminal. Marquardt analysiswas used in order to determine the effects of cimetidine and raniditine on end-plate potential kinetics. At the concentration assayed only ranitidine showed a marked blocking effect at postsynaptic level as well as a less pronounced presynaptic effect. The time course of the e.p.p.'s is also more affected by raniditine, though the kinetic behaviour observed is not a unique feature of this drug alone.

Animals↗

Cholinergic effects of cimetidine and ranitidine.

Cimetidine and ranitidine were submitted to eight in vitro assays: their intrinsic activity was evaluated on guinea-pig auricles and ileum, acetylcholine synergism on guinea-pig tracheal muscle, frog rectus abdominis, guinea-pig vas and rat phrenic nerve diaphragm, and antagonism on guinea-pig auricles and rat jejunum estimated at a range of concentrations. Ranitidine alone opposed 1-hyoscyamine antagonism in guinea-pig ileum when acetylcholine was the agonist, but not when the agonist was bethanechol.

Acetylcholine↗

[Cholinergic antagonism by beta-blockers. I. Spectrum of interactions].

Complete final steady state selective antagonism by beta-blockers of different conventional classes versus acetylcholine effects on isolated frog rectus abdominis, guinea pig ileum and spontaneous beating auricles had been measured. The results do not support common beta-blockers groupings, nor binary conventional subdivision of "nicotinic" and "muscarinic" cholinergic receptors, confirming our previous findings.

Abdominal Muscles↗