Glucocorticoid receptors, DNA synthesis, membrane antigens and their relation to disease activity in chronic lymphatic leukemia.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
L Terenius
Publications and source records attributed to L Terenius.
Endorphins in human cerebrospinal fluid.
Opiate activity in CSF samples drawn from patients with suspected intracranial hydrodynamic dysfunction has been fractionated on Sephadex G-10 and separated by column electrophoresis in agarose suspension. From the Sephadex G-10 chromatography two receptor active fractions (FI and FII) were recovered. Both FI and FII were further resolved by the electrophoresis. FI separated into at least four components and FII into two components. The study also includes a comparison of the endorphin concentrations in CSF (samples drawn from healthy volunteers) measured by receptorassay with those detected by radioimmunoassay of beta-endorphin, [Met]enkephalin and dynorphin, respectively. The data obtained indicated negligible quantities of the radioimmunoassayable endorphins in the total CSF opiate activity.
Dynorphins↗
Opioid peptide identity and localization in hippocampus.
The hippocampus contains three times as much dynorphin-17 immunoreactivity (ir) as enkephalin-ir. Hippocampal mossy fibers exhibit weak enkephalin and strong dynorphin immunostaining. Intrahippocampal colchicine injections, which selectively destroy dentate granule cells, reduce enkephalin-ir and dynorphin-ir in mossy fibers. Intraventricular kainic acid, which causes degeneration of CA3-4 pyramidal cells, results in increased enkephalin immunostaining in mossy fibers. The enkephalin-ir cells and fibers of the entorhinal cortex which innervate the hippocampus and dentate gyrus do not contain dynorphin-ir.
Animals↗
Calcitonin gene-related peptide is metabolized by an endopeptidase hydrolyzing substance P.
Calcitonin gene-related peptide (CGRP) is cleaved by an endopeptidase, also known to hydrolyze substance P (SP). The enzyme which was isolated from human cerebrospinal fluid, converted rCGRP into two products, clearly separable on HPLC. Amino acid analysis showed cleavage to occur at Leu16-Ser17. The carboxy-terminal fragment, rCGRP-(17-37), was weakly active in inhibiting 125I-rCGRP binding to a rat medulla oblongata membrane preparation, but it showed no binding to spinal cord membranes. The N-terminal fragment, rCGRP-(1-16), had very low or no affinity. Autoradiography with 125I-rCGRP showed distinct labelling of rat dorsal spinal cord, while there was no consistent pattern with 125I-rCGRP-(1-16). In the isolated guinea pig ileum preparation, the two fragments showed no CGRP-like activity. The ability of CGRP to interfere with SP degradation is offered as the explanation why CGRP has been reported to potentiate several biologic actions of SP.
Amino Acid Sequence↗
A fragment of substance P with specific central activity: SP(1-7).
Amino-terminal fragments of substance P (SP), SP(1-7) and SP(1-8), were found to produce naloxone-reversible antinociception in the mouse similar to that produced by SP. Similar to SP, these peptides produce antinociception only within a narrow dose range. They have no activity on smooth muscle or blood pressure. These results suggest that contrary to peripheral effects of SP, which are mediated by receptors which recognize the carboxy-terminal part of the SP molecule, certain central actions of SP are mediated by receptors which recognize the amino-terminal part of the SP molecule. SP may be metabolized to this active fragment prior to its action at these receptors.
Analgesia↗
Immunohistochemical analysis of the effects of cysteamine on somatostatin-like immunoreactivity in the rat central nervous system.
The brain and spinal cord of untreated and cysteamine-treated rats were analyzed with immunohistochemistry using antisera raised against somatostatin (SOM)-28(1-14) and SOM-28(15-28). Sections incubated with increasing dilutions of antiserum were evaluated subjectively on coded slides and with computer-assisted image analysis. For control experiments, antisera raised against methionine-enkephalin, neuropeptide Y (NPY) and dynorphin (DYN)(1-13) were used. The latter antiserum does not visualize the conventional DYN systems in the brain, but reacts with an unknown epitope, which here could be shown to be present in SOM neurons. In cysteamine-treated rats a marked decrease in SOM-28(15-28)-like immunoreactivity (1.1) could be recorded subjectively at all antibody concentrations in fibers in several brain areas, including nucleus accumbens, tuberculum olfactorium and the hypothalamic ventromedial and arcuate nuclei. In these areas SOM-LI is fairly weak in untreated rats. In SOM-rich regions such as the median eminence and the dorsal horn of the spinal cord, the depleting effect of cysteamine could be recorded subjectively only when diluted antisera were used. Image analysis confirmed the subjective analysis, and, in addition, differences between controls and cysteamine-treated rats could be shown also at high antiserum concentrations. SOM-28(15-28)-immunoreactive cell bodies could be seen in the brains of either control or drug-treated rats. No effect of cysteamine could be observed when antiserum raised to SOM-28(1-14) was used. Cysteamine did not seem to affect enkephalin-LI, NPY-LI or an epitope in SOM neurons reacting with DYN(1-13) antiserum. After preabsorption of SOM-28(15-28) antiserum with SOM-28(15-28) peptide, the staining patterns described above disappeared completely. However, if the SOM-28(15-28) peptide was pretreated with a high concentration (1 M) of cysteamine before being used for absorption with SOM antiserum, no blocking effect could be observed. The present results demonstrate with immunohistochemistry that cysteamine causes depletion of SOM-28(15-28) in fibers but apparently not in cell bodies. No effects on SOM-28(1-14)-LI were observed. This supports earlier evidence that cysteamine interacts with the disulphide bond in the SOM-28(15-28) molecule. The present results also emphasize that when analyzing drug effects on peptide neurons with immunohistochemical techniques, it is important to use dilution series of antibodies and preferably to carry out the analysis with objective image analysis methods.
Animals↗
Alcohol addiction (alcoholism) and the opioid system.
Alcohol interacts with many neurotransmitter systems, including the endogenous opioid peptide system, which influences the mesolimbic dopamine system and is believed to be central to drug-induced reward. These observations emphasize the need to further characterize the alcohol-opioid system link. Two important clinical studies have shown that treatment with the systemically active opioid antagonist naltrexone reduced the frequency as well as the severity of an alcohol slip (i.e., prevented relapse) among alcohol-dependent subjects who were enrolled in outpatient alcoholism treatment programs. Multiple interactions between opioid peptides and various receptors complicate our understanding of these brain mechanisms. Two possible therapeutic approaches to alcohol addiction include interfering with alcohol-induced reward and reducing sensitivity to alcohol by administering drugs that selectively block or reinforce only one selected opioid system.
Alcoholism↗
Coexistence of TRH with other neuroactive substances in the rat central nervous system.
Colocalization of thyrotropin-releasing hormone-like immunoreactivity with other neuroactive substances was examined immunohistochemically in colchicine-treated rat brains using double-staining or elution-restaining methods. Thyrotropin-releasing hormone-like immunoreactivity was shown to be located in the same neurons as: 1. enkephalin-, gamma-amino butyric acid- and tyrosine hydroxylase-, but not somatostatin-like immunoreactivity in the glomerular layer of the olfactory bulb 2. oxytocin- and cholecystokinin-, but not vasopressin-like immunoreactivity in the supraoptic nucleus 3. cholecystokinin-like immunoreactivity in posterior pituitary 4. enkephalin-like immunoreactivity in the perifornical area of the hypothalamus and 5. neuropeptide Y- and neurotensin-like immunoreactivity in the periaqueductal central grey. These findings provide further examples of coexistence of thyrotropin-releasing hormone with classical neurotransmitters and/or peptides in the rat central nervous system.
Animals↗