Search PubMed⌕ Search

Biomedical subjects

K Stengaard-Pedersen

Publications and source records attributed to K Stengaard-Pedersen.

At least 55 records · Page 3Linked to original sources
PubMed1985

Renal uric acid handling is not affected by beta-adrenoceptor blockade in normotensive subjects.

Nine normotensive healthy females received timolol 5 mg daily for a 4-day period and subsequently 20 mg daily for another 4-day period. None of the two dosages of timolol caused significant changes in serum uric acid or 24-h urinary fractional excretion of uric acid. Thus the increments of serum uric acid previously found in hypertensive patients is not likely to be caused by beta-adrenoceptor blockade per se.

Adrenergic beta-Antagonists↗
PubMed1985

Opioid peptides and receptors in relation to affective illness. Effects of desipramine and lithium on opioid receptors in rat brain.

A brief review is given of clinical and experimental evidence supporting the notion that opioid peptides and opioid receptors play a role for the regulation of mood and activity, and that they could be involved in the pathophysiology of affective illness and the action of antimanic and antidepressant treatment modalities. We have carried out in vitro and in vivo studies on the effects of desipramine and lithium on opioid receptors in rat brain. In vitro desipramine inhibited the binding of 3H-enkephalinamide to neuronal membranes (P2-fractions) through mechanisms not yet known. Treatment with desipramine in vivo (10 mg/kg body weight/day) caused a down-regulation of 3H-enkephalinamide binding in the basal ganglia and the hippocampus, while no effects could be observed in the cerebral cortex and the rest of the forebrain. In vitro addition of lithium inhibited enkephalin binding to opioid receptors through a reduction in the number of binding sites, while the affinity remained unchanged or was changed only slightly. Treatment with lithium in vivo for three weeks with lithium doses providing serum lithium concentrations of about 1 mM also caused a down-regulation in the number of opioid binding sites in the cerebral cortex, the hippocampus, and the basal ganglia, while no changes could be observed in affinity. The studies suggest that desipramine and lithium, both effective in the treatment of manic-depressive illness, may share certain actions on opioid receptors in the brain.

Animals↗
PubMed1984

Localization of enkephalin and cholecystokinin immunoreactivities in the perforant path terminal fields of the rat hippocampal formation.

The distribution of enkephalin immunoreactivity (EI) in the molecular layer of the hippocampal formation corresponded to the terminal field of the lateral perforant path and the lateral temporoammonic tract. The distribution of cholecystokinin immunoreactivity (CI) in the molecular layer of the hippocampal formation corresponded to the established terminal field of the medial temporoammonic tract. The exception was a CI band at the deep part of the molecular layer throughout the regio superior. Accordingly, an additional terminal field of the medial temporoammonic tract is suggested. Selective lesion of the entorhinal afferents to the hippocampus and the area dentata resulted in a disappearance of EI throughout the molecular layer with no affection of CI and vice versa. Neonatally X-ray irradiated hippocampi were examined as they appear in the adult animal. These animals are known to possess an altered relation between the granule cells of area dentata and the perforant path zones extending beyond a reduced medial blade into the stratum oriens of the regio inferior. In such animals EI and CI revealed the same pattern of changes by following the perforant path zones into stratum oriens due to neonatal X-ray irradiation. Accordingly, the perforant path may contain EI and CI independent of the granule cell dendrites. Based on a discussion of these observations we conclude that enkephalin immunoreactivity is localized in terminals of the lateral perforant path and the lateral temporoammonic tract and that cholecystokinin immunoreactivity is localized in the terminals of the medial perforant path and the medial temporoammonic tract.

Animals↗
PubMed1984

Modulation of cholecystokinin concentrations in the rat hippocampus by chelation of heavy metals.

Previously, we have reported that enkephalins, cholecystokinin, and heavy metals show roughly parallel distributional patterns in the hippocampus. A substantial body of evidence indicates that cholecystokinin-octapeptide (CCK-8) and enkephalins act as neurotransmitters. A CCK-8 degrading enzyme was recently detected in brain synaptosomes. Its activity depended on free thiol groups and the presence of a heavy metal. Since the heavy metal-containing neuropil is closely related to CCK-immunoreactive nerve terminals, we have investigated the effect of metal chelation on CCK components in the rat hippocampus. In vivo treatment of rats with a single dose of the chelating agent diethyldithiocarbamate caused a reversible chelation of heavy metals in the hippocampus. This effect was paralleled by a 3-fold increase in hippocampal content of CCK-8 and a smaller increase in the intermediate forms of CCK (CCK-58, CCK-39, CCK-33). Diethyldithiocarbamate also decreased the spontaneous motility and aggressiveness of the rats. These data show reversible changes of neuronal CCK processing by a drug, and hence they provide additional evidence that CCK is involved in the regulation of neuronal activities.

Animals↗
PubMed1984

Gastrin and cholecystokinin in pituitary neurons.

Gastrins occur in the hypothalamo-hypophyseal neurons of all mammalian species examined. In addition, human, bovine, and murine hypothalamo-hypophyseal neurons contain the homologous cholecystokinins (CCKs). CCK also occurs in neurons innervating bovine melanotrophs. Although the concentration of gastrin is of the same magnitude (15-30 pmol/g) in all neural lobes, the concentration of CCK varies from undetectable in pig and cat to 1 nmol/g in the cow. The constant occurrence of neurohypophyseal gastrin suggests a role different from that of the species-dependent CCK.

Animals↗
PubMed1983

Comparative mapping of opioid receptors and enkephalin immunoreactive nerve terminals in the rat hippocampus. A radiohistochemical and immunocytochemical study.

Opioid receptors can be localized to the hippocampal formation of the rat by autoradiography. The binding of 3H-enkephalinamide to fixed and mounted tissue sections has all the characteristics associated with binding to opioid receptors. It is saturable, of high affinity and displays stereospecificity. The opioid receptor distribution shows striking regional variation throughout the hippocampal formation. Areas with high density include the pyramidal cell layer of both regio superior (CA1) and regio inferior (CA3), stratum moleculare of the hippocampus, the cell layer of subiculum, the superficial part of presubiculum and the deep layer (VI) of the medial and lateral entorhinal cortices. Areas with low to medium densities include regions corresponding to the dendritic field of the pyramidal cells (str. oriens, str. radiatum and the mossy fiber zone), the dentate granule cell layer and the molecular layer of the dentate area. Enkephalin-like immunoreactivity is detected in both intrinsic neuronal systems: 1) the mossy fibers which terminate on the proximal part of the CA3 pyramidal cell dendrites and on CA4 pyramidal cells, 2) cell bodies with multiple short processes, probably interneurons, dispersed throughout the hilus of the dentate area, the pyramidal cell layer of hippocampus, the str. radiatum, and occasionally in the str. moleculare and in the str. oriens, and extrinsic neuronal systems: 1) the lateral perforant path and 2) the lateral temporo-ammonic tract. Thus, the hippocampus contains intrinsic systems of enkephalin-like immunoreactive nerve terminals which may exert their effect on the opioid receptors with a localization corresponding to the pyramidal cells and their apical dendrites. Extrinsic enkephalinergic systems corresponding to the terminal fields of the lateral perforant path and the temporoammonic tract, both of entorhinal origin, may influence the opioid receptors located in the molecular layer of the dentate area, and in the molecular layer of the hippocampus and the subiculum. Thus, the enkephalin-like immunoreactive nerve terminals are all located in areas which contain opioid binding sites. This suggests that the "opioid peptide-opioid receptor" systems may regulate hippocampal neuronal activity via neurotransmission or neuromodulation. However, a high or medium number of opioid binding sites occur over the pyramidal cell bodies and the dentate granule cell bodies, and these opioid binding sites are not in close contact with the major enkephalinergic systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

In vitro and in vivo inhibition by lithium of enkephalin binding to opiate receptors in rat brain.

The in vitro and in vivo effects of lithium ions on opiate receptor binding were studied in the cerebral cortex, the hippocampus and the basal ganglia of the rat. In vitro, lithium ions inhibited enkephalin binding to opiate receptors through a reduction in the number of binding sites, whereas the affinity was unchanged or only slightly decreased. In vivo, long term ingestion of lithium (3 weeks), during which the rats were maintained at a serum lithium level of approximately 1 mM, also inhibited enkephalin binding to rat neuronal membranes (P2-fractions) through a reduction of the number of opiate receptor binding sites, whereas the affinity was unchanged. No lithium could be detected in the suspension of neuronal membranes from the lithium-treated rats, and no difference in the concentration of endogenous opioid peptides was found between control rats and lithium-treated rats. The opiate receptors from control rats and lithium-treated rats did no display any difference in lithium sensitivity. This data suggest that administration of lithium to rats in small doses reduces opiate receptor binding of enkephalin.

Animals↗
PubMed1982

Inhibition of enkephalin binding to opiate receptors by zinc ions: possible physiological importance in the brain.

Zinc ions can totally block stereospecific binding of 3H-met-enkephalinamide (2-D-ala-5-L-methionine) to opiate receptor sites in synaptic membranes of the hippocampus, the cerebral cortex and the basal ganglia of the rat brain. Analysis of binding isotherms indicates that this inhibitory effect involves a decrease in both receptor affinity and the number of binding sites. Our data also suggest that the zinc ions react with essential SH-groups of the opiate receptor. The endogenous concentrations of zinc ions in the hippocampus, the cerebral cortex and the basal ganglia are compatible with the concentrations needed to inhibit opiate receptor binding in vitro. Especially the hippocampus contains a high concentration of zinc ion, which are localized exclusively in the giant boutons of the mossy fibers. Further, the hippocampal distribution of enkephalin and zinc ions is identical and confined to the mossy fiber zone. Hence, zinc ions may represent important modulators of opiate receptor binding in the central nervous system, particularly in the hippocampal mossy fiber zone.

Animals↗
PubMed1981

Comparative immunocytochemical localization of putative opioid ligands in the central nervous system.

We report a detailed comparative immunocytochemical mapping of enkephalin, CCK and ACTH/beta-endorphin immunoreactive nerves in the central nervous system of rat and guinea pig. Enkephalin immunoreactivity was detected in many groups of nerve cell bodies, fibers and terminals in the limbic system, basal ganglia, hypothalamus, thalamus, brain stem and spinal cord. beta-endorphin and ACTH immunoreactivity was limited to a single group of nerve cell bodies in and around the arcuate nucleus and in fibers and terminals in the midline areas of the hypothalamus, thalamus and mesencephalic periaqueductal gray with lateral extensions to the amygdaloid area. Cholecystokinin immunoreactive nerve fibers and terminals displayed a distribution similar to that of enkephalin in many regions; but striking differences were also found. An immunocytochemical doublestaining technique, which allowed simultaneous detection of two different peptides in the same tissue section, showed that enkephalin-, CCK- and ACTH/beta-endorphin-immunoreactive nerves although closely intermingled in many brain areas, occurred separately. The distributions of nerve terminals containing these neuropeptides showed striking overlaps and also paralleled the distribution of opiate receptors. This may suggest that enkephalin, CCK, ACTH and beta-endorphin may interact with each other and with opiate receptors.

Adrenocorticotropic Hormone↗
PubMed1981

Localization and opiate receptor binding of enkephalin, CCK and ACTH/beta-endorphin in the rat central nervous system.

We have examined the distributions of ACTH, CCK and enkephalin immunoreactive nerves in the rat central nervous system and compared the pattern obtained with that of opiate receptors. In addition, a radioreceptor assay has been employed for studying the possible functional interactions between these peptides and opiate receptors. Our results suggest that: (a) The distribution of enkephalin, CCK and ACTH/beta-endorphin immunoreactive nerve terminals is sufficiently similar to suggest functional interaction between these neuropeptides. (b) The CCK immunoreactive nerves display a distribution similar to that of enkephalin, but the main endogenous CCK forms do not bind to opiate receptors. However, opioid peptides and CCK may interact in many brain regions via binding to different, but functionally interacting receptors. (c) The ACTH immunoreactive nerves, which seem also to contain beta-endorphin, shows a partially overlapping distribution with the enkephalinergic systems. Further, ACTH and its fragments bind to opiate receptors. This suggests that ACTH could be an endogenous opioid ligand.

Adrenocorticotropic Hormone↗
PubMed1981

Inhibition of opiate receptor binding by zinc ions: possible physiological importance in the hippocampus.

In the rat and guinea pig hippocampus, the staining pattern for enkephalin (by immunocytochemistry) and for zinc (by the Timm method) is congruent and confined to the mossy fiber system. The stereospecific binding of 3H-enkephalinamide (2-D-Ala-5-L-methionine) to opiate receptors can be totally blocked by zinc ions, both in the hippocampus and in the cerebral cortex, the basal ganglia and the rest of the forebrain. Scatchard analysis of binding isotherms indicates that this inhibitory effect involves a decrease in receptor affinity, whereas the number of binding sites is unaffected. Thiol reductants can reactivate Zn2+-inhibited opiate receptors with a potency correlating to their redox potential (Eo). Thus, our data suggest that zinc ions represent modulators of opiate receptor binding in the hippocampus and that they work through a redox reaction with essential SH-groups of opiate receptors.

Animals↗
PubMed1981

Newly synthesized cholecystokinin in subcellular fractions of the rat brain.

The subcellular localization of in vivo synthesized cholecystokinin (CCK) in different parts of the rat brain was studied after intracisternal pulse injections of [35S]methionine. The rats were decapitated 1 h after the injection, and the brain was divided into cortex, hippocampus and remainder. Subcellular fractions were obtained according to Whittaker's method. De novo synthesized CCK in the crude mitochondrial-synaptosomal fraction, P2, and in the purified synaptosomal fraction was demonstrated by affinity chromatography, using antibodies specific for the COOH-terminal sequence of CCK. By subsequent gel chromatography two molecular forms of labelled CCK occurred, with elution constants, Kav, of 1.1 (corresponding to the COOH-terminal octapeptide) and of 1.40 (a component which may correspond to the COOH-terminal tetrapeptide amide, CCK-4). The findings support the idea that the small molecular forms are the transmitter forms of CCK.

Animals↗