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Biomedical subjects

K Fuxe

Publications and source records attributed to K Fuxe.

At least 343 records · Page 19Linked to original sources
PubMed1991

Neurotensin decreases the affinity of dopamine D2 agonist binding by a G protein-independent mechanism.

To examine whether GTP-binding proteins (G proteins) mediate the ability of neurotensin to lower the affinity of dopamine D2 agonist binding, the modulation by neurotensin in vitro of N-[3H]propylnorapomorphine [( 3H]-NPA) binding was investigated following pretreatment with pertussis toxin and N-ethylmaleimide in rat neostriatal membranes. Preincubation with N-ethylmaleimide (100 microM) markedly inhibited pertussis toxin-induced back-ADP ribosylation of three proteins with apparent molecular masses of 41, 40, and 39 kDa, respectively. This inhibition was prevented by adding dithiothreitol (250 microM) during the preincubation. N-Ethylmaleimide increased the KD (180 +/- 30%) and decreased the Bmax (-31 +/- 9%) of [3H]NPA binding sites but did not affect the binding properties of the selective D2 antagonist [3H]raclopride. N-Ethylmaleimide pretreatment did not affect the neurotensin (3 nM)-induced increase in the KD of [3H]NPA binding sites. Pertussin toxin treatment in vivo and in vitro was similarly ineffective. In conclusion, the present study indicates that neurotensin modulation of D2 agonist binding in neostriatal membranes is not mediated by G proteins.

Adenosine Diphosphate Ribose↗
PubMed1991

Changes in pituitary-adrenal activity regulate the central vasodepressor responses induced by neuropeptide Y and adrenaline in the awake unrestrained male rat.

The central cardiovascular responses induced by neuropeptide Y (0.25 nmol) and adrenaline (2.00 nmol) given i.c.v. in close to maximal doses in the awake, unrestrained male rat were studied following changes in the pituitary-adrenal activity. Adrenalectomy (1 week) alone significantly reduced the vasodepressor response to i.c.v. adrenaline but not to i.c.v. neuropeptide Y. Corticosterone replacement treatment (5 mg kg-1 x 2, i.p., 1 week) significantly reduced both the maximal (peak) and overall (area) vasodepressor responses to i.c.v. adrenaline and neuropeptide Y (only overall responses) in the adrenalectomized rat. Corticosterone treatment alone in the sham-operated rat highly significantly reduced the vasodepressor responses to both i.c.v. adrenaline and neuropeptide Y. The bradycardic action of centrally administered neuropeptide Y was no longer significant after alterations in pituitary-adrenal activity. The present results suggest that corticosterone treatment can abolish the centrally evoked vasodepressor responses to close to maximal doses of adrenaline and neuropeptide Y, which may contribute to their hypertensive properties in man. Finally, after adrenalectomy the central vasodepressor responses to neuropeptide Y dominate, since the adrenergic vasodepressor responses are selectively reduced. This dominance is reduced by corticosterone replacement treatment. The results indicate an antagonistic role of adrenocortical steroids in control of centrally induced acute vasodepressor responses to neuropeptide Y and adrenaline.

Animals↗
PubMed1991

Neurochemical effects of nicotine on glutamate and GABA mechanisms in the rat brain.

The effects of nicotine on gamma-aminobutyric acid (GABA) and glutamate mechanisms were studied in several rat brain regions both in vivo and in vitro. In vivo acute intermittent injections of nicotine decrease GABA utilization in the hypothalamus and glutamate levels within the nucleus caudatus and the subcortical limbic forebrain (mainly tuberculum olfactorium and nucleus accumbens). Glutamic acid decarboxylase activity was slightly increased in several regions, when the rats were treated with a single convulsant dose of nicotine and killed at the moment of the convulsions but it was not affected by a single injection nor by intermittent acute administration of non-convulsant doses of nicotine. In vitro nicotine elicited release of L-[3H]glutamate from synaptosomal preparations obtained from the frontoparietal cortex, nucleus caudatus and hypothalamus. The effect was dose-dependent and it was not blocked by mecamylamine. It was also Ca2+ independent. The possibilities are discussed that the decreased GABA utilization in the hypothalamus may be related to certain neuroendocrine actions of nicotine and that the nicotine-induced glutamate release might be involved in some of the physiological and toxicological effects of nicotine.

Animals↗
PubMed1991

A new model of focal brain ischemia based on the intracerebral injection of endothelin-1.

Endothelin-1 and its receptors are widely distributed in the brain of rodents and humans. In view of its potent and long-lasting vasoconstrictor activity, a role of endothelin-1 has been proposed in brain ischemia. In the present paper, the local injection of endothelin-1 was utilized to induce ischemia in rat striatum. An evaluation of the rostrocaudal extension of the lesion is reported. By using intracerebral microdialysis, a marked increase of lactate and dopamine, but not glutamate, was observed in this region upon endothelin-1 administration. Moreover, preliminary data reported show a protective effect of ganglioside treatment on endothelin-1 lesion of rat striatum. The characteristics of the present model of brain ischemia are discussed in comparison with well characterized models, such as the Pulsinelli's four vessel occlusion and the middle cerebral artery occlusion.

Animals↗
PubMed1991

Pain, analgesia, and stress: an integrated view.

The different theories on the neuroanatomical substrate of pain have been revised in the frame of new concepts on the intercellular communication in the central nervous system. In fact, it has recently been proposed that two kinds of electrochemical transmission exist in the brain: the first one, called wiring transmission (WT), uses neuronal chains (neuronal plasma membranes and synaptic contacts), whereas the second one, called volume transmission (VT), uses the extracellular fluid as physical substrate. The old concept of a separate system of afferents and central cells that constitute the pain mechanism is no more longer tenable. To reach a better understanding of the psychophysiological basis of pain, we should consider a view where WT and VT cooperate within neuronal systems functionally affected by the pervading modulatory action of endocrine signals.

Analgesia↗
PubMed1990

Evidence for a role of neosynthetized putrescine in the increase of glial fibrillary acidic protein immunoreactivity induced by a mechanical lesion in the rat brain.

The effect of alpha-difluoromethylornithine (alpha-DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) the rate limiting enzyme of polyamine biosynthesis, was studied on the astroglial reaction in a model of mechanical brain injury. alpha-DFMO markedly decreased the astroglial activation induced by the microdialysis probe implantation in the striatum of the male rat, as studied by glial fibrillary acidic protein (GFAP) immunocytochemistry. This response was restored by putrescine (20 nmol/ml) administered via the microdialysis probe. These results suggest that the astroglial reaction and the polyamine biosynthesis activation induced by a localized mechanical lesion are causally linked phenomena.

Animals↗
PubMed1990

Vasopressor effects of intracerebroventricular injections of PEC-60, a novel porcine 60-residue intestinal peptide, in the awake unrestrained male rat.

Intracerebroventricular injections (140-4300 pmol) of a 60-residue polypeptide (now designated PEC-60) isolated from pig intestine produced a dose-dependent increase (peak action 21% +/- 2; ED50 value of 1.7 nmol for the peak effect) in mean arterial blood pressure (MAP) in the awake, unrestrained male rat. The heart rate (HR) was significantly reduced with the highest doses used (1400 and 4300 pmol). The pancreatic secretory trypsin inhibitor (PSTI), with a high degree of sequence similarity to PEC-60, did not significantly change MAP and HR (4300 pmol). These results may indicate a biological role for the putative PEC-60-like peptide demonstrated within central catecholamine cardiovascular neurons.

Animals↗
PubMed1990

Intraventricular injection of neurotensin reduces dopamine D2 agonist binding in rat forebrain and intermediate lobe of the pituitary gland. Relationship to serum hormone levels and nerve terminal coexistence.

In order to investigate neurotensin-dopamine receptor interactions in vivo, the effects of intraventricular injection of neurotensin were analyzed on S(-)[N-propyl-3H(N)]propylnorapomorphine [( 3H]NPA) binding in cryostat sections of the forebrain, hypothalamus and pituitary gland, and on serum levels of prolactin, luteinizing hormone and corticosterone in the male rat. The relationship of modulation of [3H]NPA binding with neurotensin-dopamine coexistence in nerve terminals was analyzed by investigating coexistence of neurotensin and tyrosine hydroxylase (TH) immunoreactive nerve terminals in various brain areas, using a double immunohistofluorescence procedure. Intraventricular injections of neurotensin (0.03-3 nmol, 30 min) reduced dose-dependently specific [3H]NPA binding (0.25 nM) in the caudate-putamen (-38 +/- 4%), nucleus accumbens (-42 +/- 5%), tuberculum olfactorium (-52 +/- 7%) and in the intermediate lobe of the pituitary gland (-17 +/- 2%). Coexistence of neurotensin and TH was demonstrated in nerve terminals in the prefrontal, cingulate, piriform and entorhinal cortex and in the cortical and deep nuclei of the amygdaloid cortex. It was not possible to demonstrate coexistence in the caudate-putamen, nucleus accumbens, tuberculum olfactorium and median eminence, in view of the high density of dopamine nerve terminals present in relation to the few visualized neurotensin terminals. Nor could coexistence be demonstrated in the few remaining TH-positive nerve terminals following unilateral 6-hydroxydopamine lesions (8 micrograms per 4 microliters; one week) in spite of increased numbers of neurotensin-containing cell bodies and terminals in the ipsilateral dorsomedial caudate. Neurotensin injection markedly decreased serum prolactin levels and increased serum corticosterone levels by about 60%, whereas serum levels of luteinizing hormone were unaffected. The present study indicates that central dopamine D2 receptors may be regulated by neurotensin in vivo and that the neurotensin involved most likely is released from nerve terminals not containing dopamine, since fibers showing coexistence were only found in prefrontal and limbic cortical areas.

Animals↗
PubMed1990

Centrally injected neuropeptide Y (13-36) produces vasopressor effects and antagonizes the vasodepressor action of neuropeptide Y (1-36) in the awake male rat.

Intraventricular injections of the Y2 neuropeptide Y (NPY) receptor agonist porcine NPY (13-36) (pNPY (13-36); 25-3000 pmol) produced a dose-dependent increase (up to 14%; ED50 value of 0.3 nmol for overall effects and 0.97 nmol for the peak effects) in mean arterial blood pressure in the awake, unrestrained male rat without affecting heart rate. Furthermore, a subthreshold dose of pNPY (13-36) (25 pmol) counteracted the vasodepressor action of the parent compound pNPY (1-36) (75 pmol), which also acts at NPY receptors of the Y1 type. These results suggest that NPY receptors of the Y1 and Y2 type have opposing actions in central cardiovascular regulation.

Animals↗
PubMed1990

Acute and subchronic corticosterone treatment differentially modulates subcortical limbic and neostriatal nicotinic cholinergic receptors.

The effects of acute and subchronic corticosterone treatment were analyzed on the competition by (-)nicotine ((-)nicotine hydrogen(+)-tartrate) on N-[3H]methylcarbamyl choline iodide ([ 3H]MCC) binding sites in membranes from the subcortical limbic forebrain and the neostriatum. Acute treatment with corticosterone (5 mg/kg, i.p., 2 h) increased the IC50 values of (-)nicotine by 230% in the subcortical limbic areas but not in the neostriatum. Subchronic corticosterone treatment (5 mg/kg, twice a day, 7 days) increased the IC50 values of (-)nicotine by 50% and slightly decreased the specific binding of [3H]MCC (5 nM) in the subcortical limbic area. In the neostriatum, subchronic treatment with corticosterone instead decreased by 50% the IC50 values of (-)nicotine and slightly increased the specific binding of [3H]MCC. The results indicate that corticosterone treatment selectively reduces the affinity of nicotinic cholinergic receptors within the subcortical limbic forebrain.

Animals↗
PubMed1990

Autoradiographic localization of mas proto-oncogene mRNA in adult rat brain using in situ hybridization.

The cellular localization and the distribution of the mas proto-oncogene/angiotensin receptor mRNA have been studied in the male rat brain using in situ hybridization with radiolabelled mas cRNA probes. Neuronal cell populations in the forebrain were selectively labelled. A strong specific labelling was demonstrated in the dentate gyrus, the CA3 and CA4 areas of the hippocampus, the olfactory tubercle (medical part), the piriform cortex and the olfactory bulb, while a weak to moderate labelling was present all over the neocortex and especially in the frontal lobe.

Animals↗
PubMed1990

Evidence for the existence of angiotensin II like immunoreactivity in subpopulations of tyrosine hydroxylase immunoreactive neurons in the A1 and C1 area of the ventral medulla of the male rat.

By using double immunolabelling techniques the possible coexistence of tyrosine hydroxylase (TH)- and angiotensin II (ANG II)-like immunoreactivities (IR) has been studied within the noradrenaline A1 and adrenaline C1 areas of the ventral medulla of the rat. In the A1 area 20-30% of the TH IR nerve cell bodies were ANG II IR and in the C1 area 5-40% of the TH IR nerve cell bodies displayed ANG II IR. These results suggest the existence of ANG II/NA and ANG II/A costoring neurons in the A1 and C1 group, respectively, opening new possibilities for ANG II-catecholamine interactions in cardiovascular and neuroendocrine regulation.

Animals↗
PubMed1990

Neurotensin reduces the affinity of dopamine D2 receptors in membranes from post mortem human caudate-putamen.

The effects of neurotensin in vitro were investigated on the binding characteristics of N-[3H]propylnorapomorphine [( 3H]NPA) binding sites in crude membrane preparations from post mortem human caudate-putamen, obtained within 10 h after death from 3 patients without reported neurological or psychiatric diseases. Neurotensin (0.1-30 nM) was found to increase the KD value of [3H]NPA binding sites with a maximal increase of about 50% (420 +/- 45 pM) at 3 nM of neurotensin, without significantly affecting the Bmax value (123 +/- 20 pmol/g protein). These results indicate the existence of an intramembrane regulation by neurotensin receptors of D2 receptors in the human caudate-putamen.

Aged↗