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Biomedical subjects

K Fuxe

Publications and source records attributed to K Fuxe.

At least 559 records · Page 31Linked to original sources
PubMed1983

Evidence for the existence of receptor--receptor interactions in the central nervous system. Studies on the regulation of monoamine receptors by neuropeptides.

Substance P (SP) (10(-8) M) can rapidly reduce the affinity and increase the density of 3H-5-HT binding sites in spinal cord membranes. CCK-8 and CCK-4 (10(-8) M) can rapidly and differentially change the characteristics of 3H-spiperone striatal binding sites linked to DA receptors of the D2 type. CCK-4 increase and CCK-8 reduce the number of striatal binding sites for 3H-spiperone, indicating for the first time separate CCK-4 binding sites. CCK-4 (10(-8) M) but not CCK-8 (10(-8) M) can rapidly reduce the affinity and increase the number of the 3H-spiperone binding sites linked to 5-HT receptors of the dorsal cerebral cortex of rats. CCK-8 (10(-8) M) only produces a trend for a small increase in the Bmax values of these receptors. These results again imply the existence of separate CCK-4 binding sites in this case in the cerebral cortex. Glutamate (10(-6) M), but not N-methyl-D-aspartate (10(-6) M) can rapidly change the characteristics of the 3H-N-propylnorapomorphine (3H-NPA) binding sites in striatal membranes of rats. Glutamate (10(-6) M) increases the density and especially reduces the affinity of the 3H-NPA binding sites, which label D2 and D3 types of DA receptors. Taken together the present findings give evidence that neuropeptide receptors and glutamate receptors can in vitro rapidly modulate the characteristics of different types of DA and 5-HT receptors by way of receptor--receptor interactions at the comodulate level or at the local circuit level. It is hypothesized that these receptor--receptor interactions are of importance for the encoding of short-term memory.

Animals↗
PubMed1982

A new approach to quantitate the density and antigen contents of high densities of transmitter-identified terminals. Immunocytochemical studies on different types of tyrosine hydroxylase immunoreactive nerve terminals in nucleus caudatus putamen of the rat.

By means of a semi-automatic image analyzer plugged into an Apple II computer and suitable computer programs it is possible to analyze transmitter-identified nerve terminals. Thus, a densitometric approach is applied on the original photograph followed by systematic sampling which is carried out by means of a grating of circles. This procedure allows the study quantitatively of density and intensities of different types of densely packed tyrosine hydroxylase (TH) immunoreactive nerve terminals of the nuc. caudatus putamen. It is shown that the islandic TH immunoreactive nerve terminals have a higher density, but a TH content similar to the diffuse types of TH immunoreactive nerve terminals in the nuc. caudatus putamen.

Animals↗
PubMed1982

Vasopressor effects of substance P and C-terminal sequences after intracisternal injection to alpha-chloralose-anaesthetized rats: blockade by a substance P antagonist.

Substance P (SP) and the C-terminal sequences octa- and penta-SP produced dose-dependent vasopressor responses, and the action was associated with mild tachycardia. The vasopressor effect of SP was counteracted by the SP antagonist [D-Pro2,D-Phe7,D-Trp9]SP given intracisternally, suggesting that central SP receptors were involved. Experiments with different sodium contents in the vehicle and with naloxone pretreatment indicate that central naloxone-sensitive opiate receptors may exist, capable of modulating the effects of SP receptor activation.

Amino Acid Sequence↗
PubMed1982

Selective reduction of adrenaline turnover in the dorsal midline area of the caudal medulla oblongata and increase of hypothalamic adrenaline levels in the Lyon strain of genetically hypertensive rats.

Catecholamine levels and turnover have been studied in 5 week old male genetically hypertensive (LH) and normotensive (LN) rats of the Sprague-Dawley Lyon strain. The results demonstrate increased hypothalamic adrenaline levels and a reduced adrenaline turnover in the dorsal midline of the medulla oblongata (DCMO) in the LH rats compared with LN control rats. The reduction of adrenaline turnover in the DCMO may contribute to the development of spontaneous hypertension.

Animals↗
PubMed1982

Interactions of nicotine and pentobarbitone in the regulation of telencephalic and hypothalamic catecholamine levels and turnover and of adenohypophyseal hormone secretion in the normal male rat.

The effects of single intraperitoneal injections of nicotine (1 mg/kg) and the sedative-hypnotic drug pentobarbitone (30 mg/kg) alone or in combination have been studied on catecholamine (CA) nerve terminal system of the hypothalamus and the forebrain and on the adenohypophyseal hormone secretion of the normal male rat. Nicotine produced discrete reductions of dopamine (DA) levels and increases of DA turnover in striatal and limbic areas of the forebrain and increases of amine turnover in different hypothalamic noradrenaline (NA) nerve terminal systems. These effects were all antagonized by simultaneous treatment with pentobarbitone. Pentobarbitone alone, however, did not modulate CA levels or turnover in the various parts of the hypothalamus and forebrain analyzed. On the other hand, pentobarbitone increased GH and prolactin secretion and in association with tyrosine hydroxylase inhibition markedly reduced corticosterone secretion. These effects were partly counteracted by nicotine in the case of GH and prolactin secretion. Furthermore, a positive interaction appears to exist between nicotine and pentobarbitone in their actions on LH secretion. The results suggest that pentobarbitone can antagonize the actions of nicotine on CA levels and turnover in various CA nerve terminal systems of the brain leading to possible reductions in nicotine induced arousal and positive reinforcement. The neuroendocrine actions of pentobarbitone do not seem to be greatly modulated through nicotinic cholinergic receptors.

Animals↗
PubMed1982

Principles for the morphological characterization of transmitter-identified nerve cell groups.

Principles for a morphometric description of transmitter identified nerve cell groups have been introduced, exemplified on the 5-HT nerve cell group of nucleus raphe dorsalis (B7 cell group), using immunocytochemical procedures to visualize 5-HT. Both cell body parameters (mean diameter, mean perimeter, mean area, shape factor) and cell group parameters (number of cells, mean free distance among cells, volume fraction, gravity centre, major axis slope with respect to the midline) have been considered. These parameters have been obtained by the use of a semiautomatic image analyzer (Kontron MOP AMO2) plugged into an Apple II computer. By the use of this system and of suitable computer programs, it is possible to give a Cartesian representation of 5-HT nerve cell bodies in a coronal section under study. The present work has mainly one aim. To detect whether subgroups exist within a transmitter-identified cell group. Two approaches have been introduced to obtain, on objective grounds, evidence whether or not a group consists of subgroups. The first of these approaches is based on differences in cell body density within the cell group, while the second approach is based on frequency distribution analysis. This second approach is mainly sensitive to shape changes of the cell group.

Animals↗
PubMed1982

Neuroanatomical methods for the quantitative evaluation of coexistence of transmitters in nerve cells. Analysis of the ACTH- and beta-endorphin immunoreactive nerve cell bodies of the mediobasal hypothalamus of the rat.

A new statistical approach has been introduced to study in a quantitative way the coexistence of two neuromodulators in nerve cell bodies. The method has been exemplified on the ACTH-like and beta-endorphin-like immunoreactive nerve cell bodies of the mediobasal hypothalamus demonstrated by means of indirect immunofluorescence methodology. The method is based on the analysis of 3 adjacent sections which, in a random way, are stained with antiserum against neuromodulator 1, against neuromodulator 2 and with antisera against both neuromodulator 1 and neuromodulator 2. It could be shown that some neurons of the mediobasal hypothalamus do not contain at a detectable level both ACTH- and beta-endorphin-like immunoreactivity. The present method also involves an analysis of the two nerve cell groups by means of a morphometric procedure to collect additional information on the extent of coexistence. Thus, by this approach the gravity centers of the two cell groups can be calculated. The distances between the two gravity centers of the ACTH and beta-endorphin positive cell groups were significantly different at certain levels. The present method offers unique possibilities in increasing our understanding of the functional significance of coexistence of neuromodulators in one and the same nerve cell body since it makes possible a quantitative evaluation of coexistence. The usefulness of the present method is illustrated by the findings of a possible differential synthesis of ACTH- and beta-endorphin-like material in certain cell bodies of the mediobasal hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1982

Toluene and telencephalic dopamine: selective reduction of amine turnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene.

The present study demonstrates reductions of dopamine (DA) turnover in various areas of the anterior nucleus caudate of rat by toluene at concentrations lower than the current OSHA threshold limit value (100 ppm). Thus, toluene at low concentrations may produce disturbances in dopaminergic mechanisms of the basal ganglia probably leading to functional changes in sensory-motor integration. The increases in DA turnover in the cholecystokinin (CCK)-DA terminals of the subcortical limbic system induced by high concentrations of toluene may be part of the neurochemical basis for its abuse as a euphoric agent in man.

Animals↗
PubMed1982

Involvement of cholinergic nicotine-like receptors as modulators of amine turnover in various types of hypothalamic dopamine and noradrenaline nerve terminal systems and of prolactin, LH, FSH and TSH secretion in the castrated male rat.

The effects of high repeated subcutaneous doses (4 X 2 mg/kg) of nicotine have been evaluated on dopamine (DA) and noradrenaline (NA) levels and turnover in the long-term castrated male rat using catecholamine (CA) fluorescence histochemistry in combination with quantitative microfluorometry. The CA turnover was evaluated by studying the decline of the CA stores following tyrosine hydroxylase inhibition using alpha-methyltyrosine methyl ester (H 44/68). In the same experiments trunk blood was collected for the determination of serum prolactin, LH, FSH and TSH levels using standard radioimmunoassay procedures. The nicotine treatment produced a significant depletion of CA stores and an increase of CA turnover in DA and NA nerve terminals of the median eminence and in peri- and paraventricular NA systems. These effects were significantly counteracted by pretreatment with mecamylamine. Nicotine significantly reduced serum prolactin and TSH levels, and after H 44/68 it also reduced LH and FSH serum levels. These actions were counteracted by mecamylamine pretreatment, except the effects on serum TSH levels after H 44/68, which were even enhanced by pretreatment with mecamylamine. Overall intraindividual correlations showed a significant correlation between reduced CA turnover in several hypothalamic areas and increased serum LH and FSH levels, increased NA turnover in the paraventricular hypothalamic nucleus and increased serum TSH levels, and reduced DA turnover in the median eminence and increased serum LH levels. It is suggested that in the castrated male rat nicotine can activate cholinergic nicotine-like receptors facilitating DA and NA turnover and release in various hypothalamic CA nerve terminal systems including those inhibiting the secretion of prolactin and LH (DA terminals in medial and lateral palisade zone, respectively) and facilitating secretion of TSH (NA terminals in the parvocellular part of the paraventricular hypothalamic nucleus).

Animals↗
PubMed1982

New vistas on synaptic plasticity: the receptor mosaic hypothesis of the engram.

The concepts of coexistence of transmitters and of receptor-receptor interactions have increased our understanding of the integrative processes regulating synaptic homeostasis and synaptic plasticity. Depending upon the ionotropic or metabotropic characteristics of the cotransmitter, it may be mainly involved in synaptic homeostasis or synaptic plasticity, respectively. A chemical trace of the postsynaptic activity can be obtained because of the plasticity of the receptor molecules. Thus, the heuristic hypothesis is introduced that islands of receptors located on postsynaptic membranes of local circuits can be formed by means of receptor-receptor interactions favouring ordered electrotonic sequences in the local circuits. This hypothesis has been named the receptor mosaic hypothesis of the engram. The islands or clusters of receptors can then store specific and complex information and when activated by the transmitters they may induce unique changes in ion permeability and cell metabolism which, at the local circuit level, can mimic exactly a previous electrotonic sequence. They can therefore represent at least part of the engram. This hypothesis is introduced against the background of the possible existence of different types of encodings of memory.

Animals↗
PubMed1982

Effects of subchronic antidepressant drug treatment on central serotonergic mechanisms in the male rat.

These studies have examined the effects of a 2 week oral treatment with zimelidine, desipramine and imipramine in clinically relevant doses on 5-HT-1 and 5-HT-2 receptors, on 5-HT synthesis, on 5-HT dependent behaviours and on prolactin secretion in the male rat. 1. Zimelidine, desipramine and imipramine produced the same type of changes in 5-HT-1 and 5-HT-2 binding sites of the cerebral cortex. 2. A marked and selective reduction of 5-HT synthesis could be observed following long-term zimelidine treatment. 3. Long-term zimelidine and desipramine treatment reduced head twitch behaviour in mice induced by 5-HTP and 5-MeODMT. 4. Long-term treatment with zimelidine produced a reduction of basal prolactin secretion. These results suggest that long-term treatment with zimelidine desipramine and imipramine may reduce 5-HT neurotransmission at least in some 5-HT synapses in the brain which may represent part of the basis for their therapeutic activity. The indication of large numbers of low affinity binding sites (10-40 nM) for 3H-5-HT sites may lead to less steep dose effect curves and to a staprolactin secretion while long-term treatment with zimelidine results in significant reductions of prolactin secretion (11). These results support the view of the existence of a reduction of 5-HT neurotransmission at least within the hypothalamus following long-term treatment with zimelidine. Also other behavioural findings suggest that adaptive changes occur in 5-HT synapses involved in regulating the "serotonin syndrome" after long-term antidepressant treatment. Thus, the 5-HT syndrome is no longer enhanced by 5-HT uptake blocking agents. The ability of fluoxetine to enhance haloperidol-induced increases of dopamine metabolites in the striatum also disappears following chronic fluoxetine treatment (6,34).

Animals↗