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Biomedical subjects

K Fuxe

Publications and source records attributed to K Fuxe.

At least 595 records · Page 33Linked to original sources
PubMed1980

Catecholamine-stimulated cyclic AMP formation in phenylethanolamine N-methyltransferase containing brain stem nuclei of normal rats and of rats with spontaneous genetic hypertension.

Stimultaion of cyclic AMP formation by epinephrine and norepinephrine has been studied in discrete areas of rat brain that include the epinephrine-containing brain stem nuclei C-1 and C-2. In the C-1 area, epinephrine-stimulated cyclic AMP formation was partially reversed by 100 microM phentolamine and by 10--100 microM propranolol or alprenolol and hence appeared to involve activation of a mixture of both alpha- and beta-adrenergic receptors as has been reported for other rat brain areas such as the cerebral cortex. However, in the C-2-area, the epinephrine and norepinephrine stimulated cyclic AMP formation involved the activation of a single receptor type which was alpha-like in character. Stimulation of cyclic AMP formation by epinephrine in the C-2 area was antagonized by nanomolar concentrations of both phentolamine and yohimbine. The epinephrine-stimulated formation of cyclic AMP in the C-2 but not in the C-1 area was augmented in a strains of rats which exhibit spontaneous genetic hypertension (SHR) vs. Wistar-Kyoto controls. It is suggested that the enhanced epinephrine-stimulated cyclic AMP formation in the C-2 area of SHR rats could be a physiological compensatory response to some other hypertension-causing lesion which, for example, results in chronically reduced epinephrine release or in ruduced availability of epinephrine at its postsynaptic receptor thereby leading to receptor supersensitivity. Supporting this possibility was the finding that treatment of SHRs and control animals and reserpine resulted in enhancement of epinephrine-stimulated cyclic AMP formation in the C-2 area of control rats, essentially obliterating the difference between control and SHR. The findings are also interepreted as supporting the involvement of epinephrine neurons in central vaso-depressor mechanisms.

Adrenergic alpha-Antagonists↗
PubMed1980

Compensatory bilateral changes in dopamine turnover after striatal kainate lesion.

Diseases of the extrapyramidal systems like Parkinson's disease and Huntington's chorea have been closely associated with the basal ganglia. In particular, the prominent symmetrical nigrostriatal dopaminergic systems play an important role in pathogenesis and symptomatology of motor disorders. Biochemical and electrophysiological data indicate a functional relationship between the nigrostriatal pathways on the two brain hemispheres. Unilateral pharmacological manipulations result in short-term changes in contralateral dopamine (DA) release, and surgical lesions on one side lead to long-term alterations in the firing rate of contralateral dopaminergic neurones. We report here the effects of unilateral kainic acid-induced lesions of striatal cell bodies on ipsi- and contralateral striatal DA turnover. We present evidence that morphologically intact dopaminergic neurones on both sides possess compensatory mechanisms which can counteract striatal synaptic asymmetries. Such mechanisms could be responsible at least in part for the maintenance of symmetrical motor behaviour in unilaterally lesioned animals.

Animals↗
PubMed1980

On the mechanism of the antiparkinsonian action of 1-DOPA and bromocriptine: a theoretical and experimental analysis of dopamine receptor sub- and supersensitivity.

Further advancements in the development of antiparkinsonian drugs are highly dependent on a better understanding of the biochemical changes present in the "supersensitive DA receptors". The present paper stresses also the importance of the development of behavioural models for studies on supersensitive DA receptors (rotational behaviour in 6-OHDA lesioned rats) and on intact DA receptors, i.e. rotational behaviour in KA lesioned rats. The relevance of heuristic models for DA receptor sub- and supersensitivity is underlined. The pharmacological findings with bromocriptine indicate that its ability to reduce the on-off phenomenon in patients could be due to its longlasting and rather constant activation of supersensitive DA receptors, and its partial DA agonist activity at DA receptors not linked to adenylate cyclase. The concept is introduced that to understand DA receptor sub-supersensitivity it is of help to postulate variations in the numbers of coupled DA receptors as an important factor. The behavioural experiments with elymoclavine further underline this view by indicating increases in the working range at supersensitive DA receptors although the amount of agonist is reduced. Furthermore, the concept has been introduced that the DA receptor supersensitivity development does not depend only on the deficit of the transmitter but possibly also on the deficit of a presynaptically released trophic factor. This factor could play a critical role in the control of the biochemical machinery of the postsynaptic cell, e.g. receptor synthesis, formation of catalytic units and of compounds which can enhance the coupling between receptors and the biological effector.

Animals↗
PubMed1980

Renin-like immunocytochemical activity in the rat and mouse brain.

Renin-like immunoreactivity could be demonstrated in the nuclei paraventricularis, periventricularis and supraopticus of the hypothalamus and in the cerebellar cortex of rats and mice, with both the peroxidase-antiperoxidase (PAP) and fluorescence techniques. The findings are consistent with the assumption of an endogenous angiotensin-forming system in the brain.

Animals↗
PubMed1980

Toluene-induced activation of certain hypothalamic and median eminence catecholamine nerve terminal systems of the male rat and its effects on anterior pituitary hormone secretion.

Subacute exposure to high concentrations (500--1000 ppm) of toluene vapour led to an increase of noradrenaline levels in the subependymal layer of the median eminence (SEL) and to an increase of noradrenaline turnover within the subependymal layer, the paraventricular hypothalamic nucleus and the anterior periventricular hypothalamic nucleus (PV I). Increased dopamine levels in the lateral palisade zone of the median eminence (LPZ) and increased catecholamine turnover within the medial palisade zone (MPZ) were also produced. Measurement of the anterior pituitary hormone secretion showed a significant increase of FSH and delayed increase of corticosterone secretion following toluene exposure.

Animals↗
PubMed1980

Central monoamine synapses as sites of action for ergot drugs.

The acute and subacute effects of ergot drugs on central monoaminergic mechanisms were studied in the rat. The most significant findings are: 1. After acute treatment, lergotrile and bromocriptine were found to block apomorphine-induced locomotion and rearing, suggesting that these two ergot drugs can block postsynaptic DA receptors within the nucleus accumbens. 2. Several ergot drugs were shown to have high affinity for some 3H-ADTN binding sites. Earlier studies indicate that 3H-ADTN appears to label postsynaptic dopamine receptors located on nerve cells in the striatum. These ergot-sensitive 3H-ADTN binding sites appear not to be linked to the adenylate cyclase system. In addition, bromocriptine, unlike CM 29-712, was found to have a high affinity for 3H-spiperone binding sites in the striatum. 3. Bromocriptine and CM 29-712 increased norepinephrine turnover in periventricular and paraventricular hypothalamic areas, suggesting a blockade of norepinephrine receptors. CM 29-712 also increased DA turnover in the medial palisade zone of the median eminence. 4. Some ergot drugs also had affinity for 5-HT receptor binding sites, possibly reflecting a 5-HT agonistic action in some areas, as shown in behavioral studies. 5. Apomorphine and bromocriptine displaced in vivo 3H-spiperone binding in the hypothalamus, septal area, and substantia nigra, but not in the striatum. 6. Subacute treatment with bromocriptin and CM 29-712 were found to produce two types of changes in behavior: The apomorphine-induced locomotion was enhanced while the chewing and licking activity (stereotypies) was reduced. These behavioral changes may be associated with an increased affinity in the 3H-ADTN binding sites in the striatum. This treatment also produced persistent increases of DA turnover in the tuberculum olfactorium but not in striatum.

5-Hydroxytryptophan↗
PubMed1980

Aspects on receptor regulation and isoreceptor identification.

The present paper introduces a classification of receptor regulation. This classification takes into consideration especially the type of regulation (homoregulation vs. heteroregulation) and the biochemical mechanisms subserving the regulation process. Furthermore, criteria for isoreceptor identification are introduced on a quantitative basis, that is by means of comparisons of ED50 values obtained, using a certain agonist, for the different responses triggered by the binding of the ligand with the respective class of receptors. Finally, a possible case of isoreceptor interconversion is extensively discussed and a model for such an interconversion is suggested.

Binding Sites↗
PubMed1980

Mecamylamine induced blockade of nicotine induced inhibition of gonadotrophin and TSH secretion and of nicotine induced increases of catecholamine turnover in the rat hypothalamus.

Nicotine treatment of normal male rats and of ovariectomized female rats results in increases of dopamine (DA), noradrenaline (NA) and adrenaline (A) turnover in the hypothalamus, especially within the median eminence. These effects may in part mediate the inhibition of gonadotrophin and TSH secretion produced by nicotine.

Animals↗
PubMed1980

Effects of chronic treatment with l-sulpiride and haloperidol on central monoaminergic mechanisms.

Chronic treatment with l-sulpiride (20 mg/kg, twice daily) and haloperidol (0.2 mg/kg, twice daily) for 2 weeks produced behavioral signs of DA receptor supersensitivity in both the striatum and the nucleus accumbens-tuberculum olfactorium region. Thus, 48 hr after treatment apomorphine-induced locomotion, total activity, and rearing activity was significantly enhanced. These behavioral results were correlated with 10% increases in the number of binding sites for the DA agonist 3H-ADTN and the DA antagonist 3H-spiperone in striatum, but the latter sites appeared to be markedly increased in number in the subcortical limbic region. A marked loss of stereoselectivity was demonstrated in the 3H-ADTN binding site, a change that could also in part be involved in producing the signs of enhancement of DA effector mechanisms observed. A corresponding loss of stereoselectivity was not observed in the 3H-spiperone binding site to which, instead, the (+)-butaclamol had an increased affinity. Haloperidol, but not l-sulpiride, in the doses used produced a further enhancement of degeneration-induced supersensitivity at DA receptor sites.

5-Hydroxytryptophan↗
PubMed1980

Effects of chronic treatment with 1-sulpiride and haloperidol on central dopamine turnover evaluated in dopamine cell body and nerve terminal-rich areas.

Catecholamine levels and turnover have been analyzed in DA cell body and in terminal-rich areas of the midbrain, diencephalon, and forebrain 48 hr following a 2-week treatment with l-sulpiride and haloperidol. At this time interval behavioral supersensitivity to DA agonists has been demonstrated. No changes in DA turnover are found in the DA cell body groups A9 and A10 or in various DA terminals of forebrain, with a possible exception for the diffuse type of DA terminals in the tuberculum olfactorium where a reduction of DA turnover rate is observed. In the median eminence of the l-sulpiride-treated group, however, DA turnover increases are observed. It is suggested that the lack of amine turnover changes in most of the DA terminal systems of the brain is related to the development of DA receptor supersensitivity in both striatal and limbic areas, balancing the DA receptor blocking activity of the neuroleptic drugs still present in the tissue of the brain.

Animals↗