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Biomedical subjects

D Felix

Publications and source records attributed to D Felix.

At least 73 records · Page 4Linked to original sources
PubMed1987

Quantification of angiotensin iontophoresis.

A method of value for studying the effects of angiotensin II (AII) and angiotensin III (AIII) on the brain is microiontophoresis combined with single unit recording. The purpose of this study was to quantitate the release of angiotensins under various experimental conditions thus providing a firm basis for the iontophoretic application of angiotensins. Quantification of release was accomplished by adding the appropriate [3H]angiotensin to 1 X 10(-3) M solutions of AII and AIII and then measuring the counts released from the tip of the microiontophoretic pipette in vitro into a small volume of Ringer solution. Although both AII and AIII were released by diffusion from micropipettes, this release could all but be eliminated with a retaining current of 20 nA. The release of AII and AIII was linear with respect to the amount of ejecting current applied up to 60 nA, the highest current examined. Angiotensin II at pH 4.5 and AIII at pH 3.5 were released at similar rates of 41.5 and 45.1 fmol/min/nA respectively. Raising the pH of the AII solution to 4.5 reduced the rate of release to 17.9 fmol/min/nA. Transport numbers were determined as follows: AII pH 3.5-0.115; AII pH 4.5-0.035, and AIII pH 4.5-0.145. It can be concluded that angiotensins are readily released by microiontophoresis, the response is linear with respect to application current, and that with the use of the appropriate pH the rate of release of AII and AIII are comparable.

Angiotensin II↗
PubMed1987

Comparison of angiotensin II staining in rat brain using affinity purified and crude antisera.

The use of affinity purified ANG II antiserum as opposed to crude antiserum greatly enhanced the staining resolution in rat brain. This improved resolution was due to a complete loss of background staining and an apparent increase in specific staining that was totally blockable by preabsorption. With the purified antibody it was easily possible to visualise the finest fibres in rats not treated with colchicine. Furthermore, the improved technique permitted a clearer visualisation of an ANG II-like immunoreactive product in cell bodies. This use of affinity purified antibody should greatly facilitate the mapping of central angiotensinergic pathways.

Angiotensin II↗
PubMed1986

Median preoptic neurones are sensitive to blood pressure changes induced by peripheral angiotensin II.

The activity of 50 histologically identified neurones of the median preoptic area (MPO) was recorded simultaneously with blood pressure monitoring. The responsiveness of these neurones was investigated with increasing doses (25-100 ng/ml/kg) of intravenously applied angiotensin II (ANG II). Mean blood pressure rose in a dose-dependent manner (between 3.9 +/- 0.5 and 18.6 +/- 2.6 mm Hg) whereas the rise in firing frequency of MPO neurones (between 47 and 105% of spontaneous discharge) was not dose-related. The latency of neuronal response decreased according to the dose applied: at the lowest dose of angiotensin it was longer (105 +/- 20 s) than at the highest dose (26 +/- 8 s). These findings suggest that MPO neurones are sensitive to ANG II-haemodynamic changes.

Angiotensin II↗
PubMed1986

Manipulation of aminopeptidase activities: differential effects on iontophoretically applied angiotensins in rat brain.

During a recent comparison of iontophoretically applied angiotensin II (ANG II) and angiotensin III (ANG III) in the paraventricular nucleus of the rat we observed that ANG III was more potent than ANG II. This suggested that ANG II may have to be converted to ANG III before it becomes active. To test this hypothesis we performed two experiments. Firstly, we examined the effects of bestatin, an aminopeptidase B inhibitor, on the activity of applied ANG II and ANG III. Next, we monitored the effects of amastatin, a specific aminopeptidase A inhibitor, on the action of coapplied ANG II or ANG III. Bestatin, while having no activity of its own, dramatically enhanced the actions of both ANG II and ANG III. Amastatin, on the other hand, had little effect on ANG III's action and diminished or totally blocked ANG II-dependent activity. Like bestatin, amastatin had no effects alone. In total these results strongly support the notion that ANG II must be converted to ANG III in the brain before it is activated.

Aminopeptidases↗
PubMed1985

The effects of calcitonin on central neurons in the rat.

The effects of salmon calcitonin on central neurons were studied in anesthetized rats. Calcitonin applied iontophoretically consistently inhibited spontaneous activity in half of the neurons tested in the anterior hypothalamic nucleus and subthalamus but had virtually no effect on cortical and thalamic neurons. Calcitonin also inhibited glutamate-evoked activity in the neurons tested. Calcitonin administered into the brain ventricular system led to a marked decrease in spontaneous discharge of hypothalamic cells in the majority of cells tested. The onset of this response began within 20 and 30 min of calcitonin application.

Animals↗
PubMed1985

The effect of acetylcholine on neurones of the amphibian nucleus isthmi.

In the bird, histochemical and biochemical data suggest that the tectal input into nucleus isthmi is of a cholinergic nature. In the present study the response of toad (Bufo bufo gargarizans) isthmic neurones to acetylcholine was investigated using conventional extracellular recording techniques and ionophoresis. The results show isthmic cells to be strongly excited by acetylcholine (ACh), whereas neurones in the neighbouring areas show minimal sensitivity. Atropine sulphate completely blocked the response to acetylcholine and greatly decreased activity induced by visual stimulus. The present data show that acetylcholine mimics one of the physiological transmitters in the nucleus isthmi.

Acetylcholine↗
PubMed1985

Effect of cations and cation channel blockers on human natural killer cells.

We studied the influence of various extracellular Ca++ and Mg++ concentrations on human natural killer (NK) cells and found that NK cell-mediated target cell lysis requires the presence of both divalent cations. The calcium channel blocker verapamil and the local anaesthetics procaine and lidocaine inhibited NK cell-mediated killing of K 562 target cells, whereas the selective K+ channel blocker tetraethylammonium and the selective Na+ channel blocker tetrodotoxin had no effect on NK activity. Our results demonstrate an important role of extracellular Ca++ and Mg++ for NK cell-mediated killing and suggest that a free transmembrane Ca++ passage is required for target cell lysis.

Anesthetics, Local↗
PubMed1983

Chronoamperometry in vivo: does it interfere with spontaneous neuronal activity in the brain?

To test whether chronoamperometry in vivo interferes with spontaneous neuronal activity, chronoamperometric measurements were combined with electrophysiological recordings in the same preparation. Chronoamperometric measurements (0.5--1.0 V applied for 1 s) were taken in the rat corpus striatum and single unit activity was recorded extracellularly in the same area. With potentials of 0.5 V, chronoamperometric measurements did not interfere with spontaneous activity of the striatal neurons, even of those units situated in close proximity (approximately 100 micrometers) to the tip of the electrochemical working electrode. Chronoamperometric measurements at potentials from 0.6 to 1.0 V accelerated or inhibited the firing rates of part of the striatal neurons, even when the electrophysiological circuit was interrupted during the application of the chronoamperometric pulse.

Animals↗
PubMed1983

Regulation of angiotensinogen in the central nervous system.

Several interventions known to alter plasma renin substrate in rats such as nephrectomy (NX), adrenalectomy (ADX) and glucocorticoid treatment changed the angiotensinogen content in the cerebrospinal fluid (CSF) in the same direction. However, peripheral and central angiotensinogen could be dissociated from each other by ADX and NX in combination, as well as by chronic converting enzyme blockade. The regulation of brain angiotensinogen was further investigated in stroke-prone spontaneously hypertensive rats (SHR-sp) in comparison with normotensive Wistar Kyoto (WKY) rats. The angiotensinogen levels of the anterior hypothalamus and of the septal area showed strain and age-related differences. Chronic converting enzyme blockade, which kept SHR-sp normotensive, stimulated angiotensinogen in the anterior hypothalamus of both SHR-sp and WKY rats, but suppressed plasma renin substrate. A specific radioimmunoassay (RIA) for renin substrate of rat plasma also recognized the CSF angiotensinogen, and a linear correlation existed between direct and indirect measurements. In conclusion, angiotensinogen in the central nervous system appears to be immunologically similar to plasma angiotensinogen. Its regulation is not directly related, however, to circulating renin substrate, although adrenal steroids stimulate both central and peripheral angiotensinogen. A differential regulation of angiotensinogen in the brain of SHR-sp as compared to WKY is evident and could be linked to blood pressure control.

Aging↗
PubMed1982

Angiotensin-converting enzyme blockade by Captopril changes angiotensin II receptors and angiotensinogen concentrations in the brain of SHR-sp and WKY rats.

Angiotensin II-sensitive neurons in the brain of spontaneously hypertensive rats (SHR-sp) and of Wistar Kyoto rats (WKY) treated with the angiotensin-converting enzyme inhibitor Captopril were investigated for possible differences at receptor sites. Furthermore, the concentrations of angiotensinogen and renin were measured in different brain regions of these animals by biochemical assay. The higher receptor sensitivity of septal neurons to angiotensin II which existed in SHR-sp as compared to WKY was diminished by Captopril. Angiotensinogen concentrations were lower in the anterior hypothalamus but not in the septum of SHR-sp as compared to WKY. Captopril increased the level in both strains. Renin concentrations did not differ in SHR-sp and WKY. Chronic treatment with Captopril induced an increase of about 20% in septum and hypothalamic regions of SHR-sp and WKY rats. Whether these changes are causally linked to the hypertension in SHR-sp remains to be investigated.

Acetylcholine↗
PubMed1982

Increased sensitivity of neurons to angiotensin II in SHR as compared to WKY rats.

Angiotensin II (ANG II)-sensitive septal neurons in the brain of stroke-prone spontaneously hypertensive rats (SHR-sp) and of normotensive Wistar-Kyoto rats (WKY) were investigated for possible differences at receptor sites. ANG II, the competitive ANG II-antagonist saralasin, and acetylcholine (ACh), were applied microiontophoretically onto neurons of the lateral septal area. ANG II-evoked neuronal firing which was specifically inhibited by saralasin occurred at a significant lower threshold in SHR-sp (23%) and showed an extended postactivity (340%) as compared to the age-matched WKY controls. In contrast, the activity due to ACh remained similar in both strains.

Acetylcholine↗
PubMed1982

2-Aminoethanol as a possible neuromodulator in the pigeon optic tectum.

A mass fragmentographic method was used for determination of low molecular weight compounds in perfusates collected in vivo in the pigeon optic tectum by a push-pull cannula technique. 2-Aminoethanol (ethanolamine) could be collected under resting conditions (5.6 +/- 0.09 pmol/min). Electrical stimulation of optic nerve induced a 2.3-fold increase of the tectal ethanolamine outflow whereas that of GABA was not affected. Ethanolamine applied iontophoretically to tectal neurons did not influence their spontaneous discharge; however, their glutamate-induced excitation as well as the GABA-induced depression were enhanced if ethanolamine was applied simultaneously. It is suggested that optic nerve stimulation exerts a neuromodulatory effect on tectal neurons.

Animals↗
PubMed1982

Stimulation of nigrostriatal dopamine neurones by nicotine.

In rats anaesthetized with urethane, firing of neurones of the substantia nigra zona compacta was accelerated after subcutaneous or iontophoretic administration of nicotine or after iontophoretic application of acetylcholine. The excitation was prevented by iontophoretic application of dihydro-beta-erythroidine, but not by atropine. The units were identified by antidromic stimulation as neurones of the nigrostriatal system; their activity was depressed by iontophoretically applied dopamine (DA). Under the same conditions of anaesthesia, a subcutaneous injection of nicotine produced an increase in DA turnover and in homovanillic acid levels in the striatum. The effect of nicotine on striatal DA turnover was comparable to that of electrical stimulation of the nigrostriatal pathway at the average frequency seen in the firing of zona compacta neurones after systemic administration of nicotine. These observations corroborate the idea that nicotine exerts an excitatory action at the level of nigral DA nerve cells. Observations made after electrical stimulation or haloperidol under urethane anaesthesia and after nicotine in unanaesthetized rats suggest that the relatively modest effect of nicotine on striatal DA turnover is due mainly to the short duration of drug action rather than to effects of the anaesthetic on DA metabolism.

Animals↗
PubMed1982

In vitro release of endogenous beta-alanine, GABA, and glutamate, and electrophysiological effect of beta-alanine in pigeon optic tectum.

The efflux of 20 amino acids, induced by either high K+ concentration or veratrine, was determined in pigeon tectal slices. Ca2+-dependent, K+-induced release of beta-alanine, gamma-aminobutyric acid (GABA), and glutamate was observed. Veratrine caused release of the same amino acids plus glycine in a tetrodotoxin-sensitive manner. beta-Alanine had a strong inhibitory effect on the activity of tectal neurons which was blocked by strychnine but not by bicuculline. The results indicated a transmitter function for beta-alanine in the optic tectum, and were consistent with the previously proposed transmitter role of GABA and glutamate in this structure.

Alanine↗
PubMed1982

Suppressive action of picrotoxin, a GABA antagonist, on labyrinthine spontaneous nystagmus and vertigo in man.

There is evidence that GABA acts as the excitatory neurotransmitter at synapses between vestibular hair cells and the afferent fibres in the mammalian labyrinth. The question arose as to whether certain vestibular dysfunctions such as labyrinthine vertigo could be treated in patients by influencing the peripheral GABA system by means of the GABA antagonist picrotoxin, a well known analeptic drug. With the application of slow infusion rates of only milligrams of picrotoxin a distinct suppression of peripheral spontaneous nystagmus, caloric excitability of labyrinths, and labyrinthine vertigo, without general CNS-induced arousal effect, was observed. A latent central spontaneous nystagmus can become manifest, whereas a manifest central spontaneous nystagmus remains unchanged. A future application of picrotoxin as a diagnostic and therapeutic tool in cases involving vestibular disorders is discussed.

Dose-Response Relationship, Drug↗