1,721,008 research outputs found
Controllo della concentrazione plasmatica dei farmaci
Aspetti teorici e pratici sull'impostazione di regimi terapeutici basati sulle proprietà farmacocinetiche dei farmac
Basi cellulari della farmacocinetica
Basi cellulari e fisiche del passaggio di farmaci tra compartimenti e delle cinetiche relativ
Assorbimento e vie di somministrazione dei farmaci
Cinetiche di assorbimento, limiti, vantaggi e aspetti pratici delle delle diverse vie di somministrazione dei farmac
Distribuzione ed eliminazione dei farmaci
Cinetiche, meccanismi, basi cellulari e sistemiche e aspetti pratici relativi alla distribuzione e all'eliminazione dei farmac
Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT1A and 5-HT1D receptors
We have recently shown that the mitogenic effect of serotonin (5-hydroxytryptamine, 5-HT) on human small lung carcinoma (SCLC) cells is at least partly due to stimulation of a 5-HT1D receptor type. We now report that the 5-HT1A receptor agonist R(+)-8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT) is also capable of stimulating [3H]thymidine incorporation into SCLC GLC-8 cells, although with lower efficacy than 5-HT. The simultaneous administration of maximal doses of 8-OH-DPAT and the 5-HT1D receptor agonist sumatriptan reproduced the maximal [3H]thymidine incorporation observed with 5-HT alone. The 5-HT1A receptor antagonists spiperone and SDZ 216-525 completely abolished the effect of 8-OH-DPAT (IC50 30 nM for both drugs) behaving as pure antagonists. Accordingly, the two drugs partially inhibited the mitogenic effect of 5-HT. These data indicate that the mitogenic effect of 5-HT in SCLC cells involves both 5-HT1A and 5-HT1D receptor types
Effects of the neuronal phosphoprotein synapsin I on actin polymerization. I. Evidence for a phosphorylation-dependent nucleating effect
Exposure to reduced gravity impairs junctional transmission at the semicircular canal in the frog labyrinth
The effects of microgravity on frog semicircular canals have been studied by electrophysiological and morphological approaches. Reduced gravity (microG) was simulated by a “random positioning machine” (RPM) which continually and randomly modified the orientation in space of the anesthetized animal. As this procedure stimulates the semicircular canals, the effect of altered gravity was isolated by comparing microG-treatment with an identical rotary stimulation in the presence of normogravity (normoG). Electrophysiological experiments were performed in the isolated labyrinth, extracted from the animals after the treatment and mounted on a turntable. Junctional activity was measured by recording quantal events (mEPSPs) and spikes from the afferent fibers close to the junction, at rest and during rotational stimulation. MicroG treated animals displayed a marked decrease in the frequency of resting and evoked mEPSP discharge, versus both control and normoG (mean decrease ~50%). Spike discharge was also depressed: 57% of microG-treated frogs displayed no spikes at rest and during rotation at 0.1 Hz, vs. 23-31% of control or normoG frogs. Among the firing units, during one cycle of sinusoidal rotation at 0.1 Hz microG treated units emitted an average of 41.8 +/- 8.06 spikes, vs. 77.2 +/- 8.19 in controls. Patch-clamp analysis on dissociated hair cells revealed altered Ca2+ handling, after microG, consistent with and supportive of the specificity of microG effects. Marked morphological signs of cellular suffering were observed after microG, mainly in the central part of the sensory epithelium. Functional changes due to microgravity were reversible within a few days
Study of rotation frequency dependence of EPSP rate at the cytoneural junction of frog labyrinth
The frequency response of the cytoneural junction was studied in the frog labyrinth posterior canal by recording EPSPs in response to sinusoidal rotation at various frequencies (0.02-1 Hz) in the presence of tetrodotoxin. Peak accelerations ranged from 3 to 63 deg/s2 but were kept constant (15 deg/s2 ) in some units by changing rotation amplítudes and frequencies. EPSP waveform was evaluated from power spectra and EPSP rate was determined by means of a fluctuation analysis procedure devised to study responses as fast as the changes in EPSP rate during rotation at 1 Hz. At all rotation frequencies the responses were asymmetric, the increase in EPSP rate for excitatory acceleration being 1.2-2.5 larger than the decrease during the corresponding inhibitory acceleration. Asymmetrical sinusoids well fit all responses. Frequency responses were obtained for each unit in terms of: 1)GAIN (change in EPSP rate vs. acceleration);. 2)PHASE (phase lead vs. angular velocity); 3)ASYMMETRY (ratio between positive and negative responses). At constant acceleration the relation of gain vs. frequency was described by a low-pass filter function (corner frequency range 0.05-0.14 Hz). This is in agreement with the behaviour predicted by the cupula-endolymph system. When peak accelerations were changed the responses, normalized to peak acceleration, displayed the same behaviour (corner frequency 0.05¬0.19 Hz); phase leads were generally in agreement with the model. Asymmetry in the response did not exhibít any clear-cut frequency dependence. In conclusion, these data indicate that most of the static and dynamic properties usually described for the spike discharge pattern directly derive from the properties of neurotransmitter release at the cytoneural junction
Voltage- and activity-dependent chloride conductance controls the resting status of the intact rat sympathetic neuron
Remarkable activity dependence was uncovered in the chloride conductance that operates in the subthreshold region of membrane potential, by using the two-microelectrode voltage-clamp technique in the mature and intact rat sympathetic neuron. Both direct and synaptic neuron tetanization (15 Hz, 10-s duration to saturate the response) resulted in a long-lasting (not less than 15 min) increase of cell input conductance (+70-150% 10 min after tetanus), accompanied by the onset of an inward current with the same time course. Both processes developed with similar properties in the postganglionic neuron when presynaptic stimulation was performed under current- or voltage-clamp conditions and were unaffected by external calcium on direct stimulation. The posttetanic effects were sustained by gCl increase because both conductance and current modifications were blocked by 0.5 mM Anthracene-9-carboxylic acid (a chloride channel blocker) but were unaffected by TEACl or cesium chloride treatments. The chloride channel properties were modified by stimulation: their voltage sensitivity and rate of closure in response to hyperpolarization strongly increased. The voltage dependence of the three major conductances governing the cell subthreshold status (gCl, gK, and gL) was evaluated over the -40/-110 mV membrane potential range in unstimulated neurons and compared with previous results in stimulated neurons. A drastic difference between the voltage-conductance profiles was observed, exclusively sustained by gCl increase. The chloride channel thus hosts an intrinsic mechanism, a memory of previous neuron activity, which makes the chloride current a likely candidate for natural controller of the balance between opposite resting currents and thus of membrane potential level
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