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Biomedical subjects

D Felix

Publications and source records attributed to D Felix.

At least 19 recordsLinked to original sources
PubMed1992

Effects of angiotensin II and its selective antagonists on inferior olivary neurones.

On the basis of biochemical and autoradiographic studies it has been shown that the inferior olivary nucleus (ION) contains predominantly angiotensin II (Ang II) receptors of the subtype 2 (AT2). In the present investigation we used microiontophoretic techniques to test the effect of Ang II on the spontaneous firing rate of rat neurones in the ION in vivo. Ang II excited the majority of histologically identified ION neurones. Furthermore, the antagonism of this angiotensin-induced excitation by selective angiotensin receptor blockers of subtype 1 and 2 (AT1 and AT2) was examined. The excitation could be blocked by low doses of the AT2-antagonists PD 123177 and CGP 42112A, whereas the AT1-antagonist DuP 753 was ineffective even at high doses. On a few occasions, however, ejection of the AT1-antagonist resulted in a potentiation of angiotensin-induced excitation. The results suggest that Ang II has an excitatory effect on a considerable number of ION neurones and that this effect is mediated by AT2-receptors.

Angiotensin II↗
PubMed1992

Effects of angiotensin analogues and angiotensin receptor antagonists on paraventricular neurones.

In a previous study we observed that most neurones in the paraventricular nucleus are excited by angiotensin-(1-7). In comparison with angiotensin III this excitatory action was significantly delayed. The aim of the present microiontophoretic study of angiotensin II-sensitive rat paraventricular neurones was to compare the effect of the angiotensin-analogues angiotensin-(1-7), angiotensin-(2-7), angiotensin II and angiotensin III on the spontaneous activity of these neurones and to test angiotensin receptor subtype 1 antagonists (CGP 46027 or DuP 753) and subtype 2 selective antagonists (CGP 42112A and PD 123177) in order to acquire more evidence of the receptor subtype present. As previously observed angiotensin II, angiotensin III and angiotensin-(1-7) excited most neurones. The effect of angiotensin-(1-7) was usually weaker than that of angiotensin II, and in contrast to angiotensin III the latencies were not significantly different. Angiotensin-(1-7) seemed to be active by itself, because its effect was antagonised by angiotensin receptor antagonists. Angiotensin-(2-7) was mostly inactive, although a few cells were excited. Whereas the excitatory effects of angiotensin-(1-7), angiotensin II and angiotensin III could always be inhibited with both angiotensin receptor subtype antagonists 1 and 2, that produced by angiotensin-(2-7) was only weakly antagonised, if at all. Subtype 1 selective antagonists were effective at lower concentrations than selective subtype 2 antagonists.

Angiotensin II↗
PubMed1992

Caroverine depresses the activity of cochlear glutamate receptors in guinea pigs: in vivo model for drug-induced neuroprotection?

With the aid of microiontophoretic techniques the action of caroverine, a quinoxaline-derivative, was tested on the receptor-linked depolarisation of the subsynaptic membrane of cochlear afferents. This membrane can be depolarised by the afferent transmitter agonist glutamate, mediated by NMDA and non-NMDA receptors and by acetylcholine, one of the different transmitter substances, released physiologically on axodendritic efferent synapses. Caroverine antagonized the membrane response to glutamate in an enduring but reversible manner. In contrast, the drug exhibited no effect on the depolarising action of acetylcholine. Therefore, the pharmacological profile of caroverine corresponded to the action of selective glutamate receptor antagonists. Since glutamate is likely to be the major mediator of neurotoxicity in the central nervous system, the selective glutamate-antagonism of caroverine is of particular interest, due to its putative neuroprotective competence. Caroverine is currently available clinically in some countries as a spasmolytic drug. Following these results it is proposed to test the drug for clinical efficacy in putatively glutamate-induced, excitotoxic disorders of the brain.

Animals↗
PubMed1992

The efferent modulation of mammalian inner hair cell afferents.

The results of immunocytochemical, enzymatic and electrophysiological studies have indicated that acetylcholine and GABA may act as neurotransmitters in lateral olivocochlear efferent endings on inner hair cell afferent dendrites. Since spike activity can be recorded in the dendritic region of inner hair cells, microiontophoretic techniques were used testing the possible neurotransmitter candidates, acetylcholine and GABA, on spontaneous and induced firing of the afferent dendrites. The experiments were carried out in anaesthetised guinea-pigs, the third and fourth turns of the cochlea being exposed for electrode penetration. Ejection of acetylcholine resulted in a pronounced dose-dependent increase in subsynaptic spiking activity. Furthermore, acetylcholine enhanced glutamate-induced activity. In contrast, even at high doses, GABA had very little effect on the spontaneous cochlear firing rate. When the firing rate had first been enhanced by glutamate or N-methyl-D-aspartate, however, this activation could be reduced by the ejection of GABA. A similar reduction was observed when the firing rate had been enhanced with acetylcholine. The results of our studies support the hypothesis that these substances are involved in efferent neurotransmission on inner hair cell afferent fibres. It should be pointed out, however, that besides acetylcholine and GABA, several opioids such as enkephalins and dynorphins seem to be involved in efferent cochlear innervation.

Acetylcholine↗
PubMed1991

An immunocytochemical comparison of the angiotensin and vasopressin hypothalamo-neurohypophysial systems in normotensive rats.

In the present study we investigated the possibility that angiotensin II/III and vasopressin coexist in the hypothalamo-neurohypophysial pathway. For our experiments 8-week-old male rats not treated with colchicine were used. The anatomical orientation of the entire pathway for angiotensin and vasopressin was facilitated by examining a series of subsequent coronal, horizontal and sagittal sections. Arching fibre tracts are formed mainly by projections emanating from cell bodies in the paraventricular nucleus, the accessory magnocellular nuclei, the supraoptic nucleus and the retrochiasmatic part of the supraoptic nucleus. The majority extend as far as the median eminence and the neurohypophysis, where major terminal fields exist. However, there is a difference between the staining pattern within the suprachiasmatic nucleus and the hypophysis. The results clearly show the colocalization of angiotensin and vasopressin in neurones as well as in fibres of the hypothalamo-neurohypophysial system.

Angiotensin II↗
PubMed1991

N-methyl-D-aspartate-induced oscillations in excitatory afferent neurotransmission in the guinea pig cochlea.

With the aid of microiontophoretic techniques we tested the action of N-methyl-D-aspartate (NMDA) and an NMDA antagonist in the dendritic region of inner hair cell afferent fibers. In the majority of units tested NMDA enhanced the spontaneous firing rate. Furthermore, the activation of NMDA receptors triggered unusual depolarization patterns: (1) slow-frequency oscillation with a periodicity of about 3/min; (2) a fast oscillatory pattern of burst firing with a rhythmic interburst frequency of about 2/s. These findings provide evidence for NMDA receptor properties in the cochlea similar to those of analog channels in the central nervous system.

Action Potentials↗
PubMed1991

Glutamate receptors in afferent cochlear neurotransmission in guinea pigs.

With the aid of microinotophoretic techniques we tested the action of the transmitter candidate glutamate (Glu) at the afferent synapses of inner hair cells (IHC) in guinea pigs. In order to determine the various types of glutamate receptors, further agonistic excitatory amino acids (EAA) as well as competitive EAA-antagonists were used. Applied perisynaptically, Glu, aspartate, N-methyl-D-aspartate (NMDA), quisqualate (Q) and kainate (K) activate the subsynaptic, phasic firing activity of the afferent dendrites. The NMDA-induced activation is augmented by simultaneous application of glycine. The firing rate induced by Glu and NMDA is blocked by the specific NMDA-antagonist D-2-amino-7-phosphonoheptanoate (AP-7). Furthermore, activity induced by Glu and Q decreases under the influence of the selective Q-antagonist glutamic acid diethylester (GDEE). These results are consistent with the hypothesis that Glu acts as a possible afferent neurotransmitter of the IHC. This neurotransmission is mediated by postsynaptic EAA-receptor subpopulations which are sensitive to NMDA, Q and K. The activity of the NMDA-receptors depends, however, on the amount of glycine available. Our data suggest that the afferent synapses of the IHC possess functional properties which are equivalent to the properties of glutamatergic NMDA-sensitive and NMDA-non-sensitive synapses in the central nervous system.

Afferent Pathways↗
PubMed1979

Spike activity and histofluorescence correlated in the giant dopamine neurone of Planorbis corneus.

The relationship between catecholamine fluorescence and electrical activity of the nerve cell has been investigated in the giant dopamine neuron (GDN) of the left pedal ganglion of the European water snail, Planorbis corneus. Electrical recordings were performed in vitro with intracellular microelectrodes on 35 GDN. The ganglion was frozen to -195 degrees C with the electrode in situ and processed for histochemical microfluorimetry. The intensity of catecholamine fluorescence was measured over different places (42/cell) throughout the cytoplasm of the GDN. In order to investigate the temporal relation between histochemical and electrophysiological parameters, the activity of 21 GDN was changed by administration of nicotine to the bathing solution (10(-5)--10(-7) M). This treatment was followed by depolarization in most of the GDN, with increased firing in two thirds and decreased activity in one third of the spontaneously active cells, whereas hyperpolarization was seen in 4 GDN, accompanied by a decrease in firing. Acetylcholine (10(-5) M) tested on one GDN caused depolarization and increased firing. A signigicant positive correlation was found between the fluorescence intensity of individual GDN and the firing rate of these cells as observed during the last 60 sec or the last 10 sec before freezing. The correlation coefficient dropped markedly when the first rates of the 2nd, 3rd, or 4th and 5th min before freezing were correlated with cellular fluorescence intensity. Intensity was not correlated with the resting membrane potential recorded at the time of freezing. The intensity response to activation was not uniform throughout the cytoplasm of GDN. Neurons with increased mean fluorescence intensity regularly showed small clusters and cristae of intensely fluorescent material surrounded by less fluorescent parts of the cytoplasm. This morphological observation of increased intensity differences between cytoplasmic structures was confirmed by the statistics of the intensity values determined in individual cells. The present observations demonstrate the existence of a relation between cell firing and neuronal dopamine fluorescence at the level of the individual nerve cell. The activity immediately preceding the time of freezing of the cell appears to be most important. Certain components of the cytoplasm appear to react preferentially; their subcellular nature remains to be elucidated. The link between electrical activity and cellular dopamine fluorescene was found to be basically the same in the giatn invertebrate neuron and in the dopamine nerve cells of rat substantia nigra.

Animals↗
PubMed1978

Angiotensin receptive neurones in the subfornical organ. Structure-activity relations.

A microiontophoretic study was performed of the actions of angiotensin II and angiotensin fragments on neurones of the subfornical organ (SFO). Adult cats were anaesthetized and the SFO exposed for penetration by a multibarrelled micropipette. We found that angiotensin II-[2--8]-heptapeptide shows a significantly higher stimulation of firing rate compared to angiotensin II. Angiotensin II-[5--8]-tetrapeptide still produced an excitatory action on a single units. Both the action of the heptapeptide and the tetrapeptide were blocked by [sar1, Ala8]-angiotensin II (P 113). In contrast, angiotensin II-[6--8]-tripeptide failed to enhance the firing rate of the same neurones. Our data indicate that angiotensin II and some shorter chain peptide fragments can directly affect neurones of the SFO. The study may give new insight in structure-activity relations for angiotensin II. The results support the hypothesis that the subfornical organ is a receptor site which is available to this peptide.

Acetylcholine↗
PubMed1977

Hypothalamic changes during the immune response.

The immune system is subject to an array of identified autoregulatory processes, but immunoregulation may also have a further basis in a network of immune-neuroendocrine interactions. Two antigens each produced an increase of more than 100% in electrical activity of individual neurones in the ventromedial but not in the anterior nucleus of the rat hypothalamus. Animals that failed to respond to antigen manifested no increase in the firing rate. These findings constitute the first evidence for a flow of information from the activated immune system to the hypothalamus, suggesting that the brain is involved in the immune response.

Action Potentials↗
PubMed1976

A quantitative correlation between single unit activity and fluorescence intensity of dopamine neurones in zona compacta of substantia nigra, as demonstrated under the influence of nicotine and physostigmine.

In order to investigate the possible relationship between neuronal activity and cellular fluorescence intensity, extracellular recordings of single unit activity and determinations of fluorescence intensity of dopamine (DA) neurones by histochemical microfluorimetry were performed in the same (rostral) part of zona compacta of substantia nigra in male rats. In urethane anaesthesia, zona compacta neurones characteristically showed a slow and fairly regular type of firing. Nicotine (1 mg/kg s.c.) induced a transient decrease in unit activity for 1 min followed by a sustained increase in firing rate. During that stage, 4-5 neurones/rat were recorded at different anteroposterior levels, each during 200 sec. Microfluorimetric examination of the fluorescence intensity developed at the end of the 30-min observation period by the DA neurones of the same area revealed a marked rise in cellular fluorescence intensity. Similar results were obtained with a lower dose of nicotine and/or a shorter observation period. Additional microiontophoretic experiments supported the view that extracellular recordings of the correlative electrophysiological-microfluorimetric investigation belonged to DA neurones. Release of DA from terminals was indicated by an increase in HVA concentration of caudate-putamen in rats subjected to the same nicotine treatment. When tested on one cell during a prolonged period of time, physostigmine (0.25 mg/kg i.p.) caused an initial increase in firing rate of zona compacta neurones (5-10 min) followed by a decrease of unit activity (15-23 min). In agreement with previous observations in mice, fluorescence intensity of nigral DA neurones likewise showed a biphasic change with an initial rise and subsequent decrease (examined at 9.5 and 22-23.5 min, respectively). When mean unit activity and mean fluorescence intensity of individual rats out of various experimental groups were related to each other, a highly significant positive correlation between neuronal fluorescence intensity and firing rate was found. The results obtained with physostigmine demonstrate that mean intensity closely paralleled mean unit activity in time, so that this correlation was maintained. These findings indicate that cellular fluorescence intensity of DA neurone groups can be used as an index of the level of neuronal activity, except for cases where a drug treatment interferes directly with catecholamine synthesis or storage mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Specific angiotensin II receptive neurons in the cat subfornical organ.

To test if neurons in the subfornical organ (SFO) are specifically sensitive to angiotensin II (AII) we have applied the AII analog sar1-ala8-AII (P113) directly on to cells in the SFO by microiontophoresis. Adult cats were anesthetized and the SFO exposed for penetration by a 5-barreled micropipette electrode. Of 22 units which responded positively to AII, 7 were also positive to acetylcholine. P113 alone produced either no effect or a decrease in unit firing. P113 plus AII produced antagonism in 17 of 18 units. P113 plus acetylcholine produced antagonistic effects in 5 of 14 cases. Only two units were completely antagonized and 5 units showed agonistic interaction. The most sensitive antagonism with respect to dose of P113 was on neurons responsive only to AII and not to both AII and acetylcholine. We conclude that there are specific AII neurons in the SFO.

Acetylcholine↗
PubMed1976

Peptide and acetylcholine action on neurones of the cat subfornical organ.

Angiotensin II, related oligopeptides and acetylcholine were tested on neurones of the cat subfornical organ (SFO). Angiotensin II activates SFO-neurones by local administration onto the surface, by i.v. injection or with the aid of microiontophoretic techniques. Application of related oligopeptides, bradykinin, physalaemin and eledoisin showed no comparable results. Activation of neurones similar to those observed after angiotensin II was obtained with acetylcholine. About 30% of the cells tested were excited by both substances, 56% of tested SFO-cells responded only to angiotensin II, but not to acetylcholine. Atropine sulphate prevents specifically the acetylcholine excitation. Since angiotensin II is involved in regulatory mechanism of thirst, these results suggest the possibility that the SFO is one of the sites, where dipsogenic receptors for this circulating peptide are located.

Acetylcholine↗