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Biomedical subjects

L Terenius

Publications and source records attributed to L Terenius.

At least 253 records · Page 14Linked to original sources

Differential co-existence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system of the rat.

The distribution of neuropeptide Y immunoreactive cell bodies in relation to various types of catecholamine-containing cell bodies in the rat brain was analyzed immunohistochemically using antisera to tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase. Coexistence of the peptide in catecholamine cell bodies was established by using an elution-restaining procedure. Neuropeptide Y-like immunoreactivity was observed in most noradrenergic cell bodies of the Al/Cl cell groups in the ventro lateral medulla oblongata. Similarly this peptide immunoreactivity was also observed in the majority of the adrenergic cell bodies of the C2 group. In the dorsal and dorsal-lateral part of the nucleus of the solitary tract, where a group of small adrenergic cells is present, several small neuropeptide Y immunoreactive cells were also observed. The possibility of coexistence of adrenaline and neuropeptide Y in these cells remains to be established. The majority of the noradrenergic cell bodies of the A2 group, as well as the presumptive dopaminergic cells within its ventromedial part, seemed to lack neuropeptide Y-like immunoreactivity. Many noradrenergic cell bodies of the A6 group in the locus coeruleus proper were neuropeptide Y-immunoreactive, whereas the peptide could not be observed in the subcoeruleus group. Neither the A5 and A7 noradrenergic cells in the pons, nor any of the dopaminergic cell groups in the mesencephalon and forebrain (A8-A15) seemed to contain a neuropeptide Y-like peptide. The findings indicate that central catecholamine neurons can be subdivided into distinct sub-groups based upon the coexistence of a specific peptide.

Animals↗

Dynorphin-immunoreactive neurons in the autonomic nervous system.

The distribution of dynorphin-like immunoreactivity in the autonomic nervous system of the rat and guinea-pig was investigated using an antiserum raised against dynorphin-(1-17). Dynorphin-like immunoreactivity was observed in fiber networks in the prevertebral sympathetic ganglia, in fibers in the enteric plexa , circular muscle layer and a few in the lamina muscularis of the mucosa of the gastrointestinal tract. After colchicine treatment dynorphin-immunoreactive cell bodies were observed both in the myenteric and submucous ganglia of the gut. The paravertebral ganglia contained occasional dynorphin-positive fibers and a few immunoreactive small intensely fluorescent cells. The distribution of the dynorphin-like immunoreactivity was compared to the distribution of enkephalin-like immunoreactivity, and it was found that in some areas there were similarities in the distribution patterns, although in other areas there were clear differences, indicating a non-identity of these two systems.

Adrenal Glands↗

CSF and plasma beta-casomorphin-like opioid peptides in postpartum psychosis.

The authors measured opioid receptor-active components in the CSF of 11 women with postpartum psychosis, 11 healthy lactating women, and 16 healthy women who were not lactating. Activity that eluted with 0.2 M acetic acid 0.7-0.9 times the total volume of the column (fraction II activity) was significantly higher in the CSF of both healthy and psychotic women in the puerperium than in that of the lactating women. Very high levels of fraction II activity were seen in four psychotic patients. Material from these patients was further characterized by electrophoresis and high-performance liquid chromatography: The material migrated as bovine beta-casomorphin. Receptor-active material with the same characteristics was also found in the plasma of these four patients. The authors conclude that certain cases of postpartum psychosis are associated with the occurrence in plasma and CSF of unique opioid peptides probably related to bovine beta-casomorphin.

Adult↗

Transmitter and peptide systems in areas involved in the control of blood pressure.

The distribution of catecholamine neurons in the dorsal vagal complex is described on the basis of indirect immunofluorescence histochemistry using antisera to three enzymes in the catecholamine synthesis, tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase, allowing differentiation between dopamine, noradrenaline and adrenaline cells. In addition attention was focused on the occurrence of two peptides, neuropeptide Y (NPY) and neurotensin in this region. It could be established that they partly were present in subpopulations of the A2/C2 catecholamine neurons. The significance of this coexistence of a peptide and a catecholamine is discussed.

Animals↗

Elevation of substance P-like peptides in the CSF of psychiatric patients.

Using a radioimmunoassay procedure substance P-like activity was measured in samples of human CSF obtained from 12 patients with major depressive disorder, 12 with schizophrenia, and 15 control cases diagnosed as psychiatrically normal. Levels were significantly higher in CSF of patients with depressive disorder as compared with schizophrenic patients or controls. Chemical characterization revealed that the measured activity was less basic than substance P itself and might be due to C-terminal fragments. A component reacting with an antiserum highly specific for the substance P[1-7]fragment was found in CSF of patients with depressive disorder. The results indicate that substance P-related peptides may be biological markers in psychoses, particularly in major depressive disorder.

Adult↗

Comparative immunohistochemical and biochemical analysis of pancreatic polypeptide-like peptides with special reference to presence of neuropeptide Y in central and peripheral neurons.

Antisera raised against porcine neuropeptide Y (NPY) and peptide YY (PYY) were characterized with regard to immunohistochemical staining, cross-reactivity to several pancreatic polypeptide (PP)-related peptides, and radioimmunoassayable tissue levels in the rat and pig. The NPY antiserum (102B) reacted with nerves in many areas of both the central and peripheral nervous systems, but it did not stain endocrine cells of the pancreas or intestine. No evidence for any cross-reactivity of the NPY antiserum with related peptides of the PP family, such as avian PP, bovine PP, PYY, gamma-MSH, FMRF-amide, or avian PP (31-36), was obtained. The NPY antiserum was N-terminally directed, and regional levels of NPY as seen by radioimmunoassay paralleled well the occurrence of NPY-immunoreactive structures seen in the immunohistochemical study. High pressure liquid chromatography analysis revealed that the NPY-immunoreactive material from cerebral cortex and vas deferens had elution profiles similar to those of standard porcine NPY. The PYY antiserum mainly stained endocrine cells in the pancreas and intestine as well as a small neuron system in the brainstem of the rat. Although this antiserum had a slight cross-reactivity to NPY in radioimmunoassay, the neuronal PYY staining was separate from that of NPY. High levels of PYY were found in the intestine, and levels above the threshold were also seen in the dorsal vagal complex of the rat. The other antisera investigated (raised against avian PP, bovine PP, gamma-MSH, and FMRF-amide) caused neuronal staining that was abolished by preabsorption with NPY. This was also seen even if no detectable cross-reactivity with NPY was found in radioimmunoassay. These latter antisera also stained endocrine cells in the pancreas and intestine with complex cross-reactivity relationships, suggesting the presence of intestinal PP-like peptides in addition to PYY and NPY.

Animals↗

Separate origins for the dynorphin and enkephalin immunoreactive fibers in the inferior mesenteric ganglion of the guinea pig.

By different denervation procedures the origin of dynorphin-(1-17) and enkephalin immunoreactive fibers in the guinea pig inferior mesenteric ganglion was investigated. It was found that the dynorphin-(1-17)-positive fibers reached the ganglion predominantly via the colonic nerves and to a lesser extent via the hypogastric and intermesenteric nerves whereas the enkephalin-positive fibers reached the ganglion via the lumbar splanchnic nerves. These findings show that the dynorphin-(1-17) and enkephalin systems are separate in this ganglion.

Animals↗

High levels of neuropeptide Y in peripheral noradrenergic neurons in various mammals including man.

Using a highly specific radioimmunoassay for neuropeptide Y (NPY), levels in the peripheral nervous system of guinea-pig, cat, pig and man were measured. In all species very high levels (up to 800 pmol X g-1) were found in sympathetic ganglia and in tissues which receive a dense sympathetic innervation, such as vas deferens, heart atrium, blood vessels and spleen. By immunocytochemistry, NPY-immunoreactive (-IR) principal ganglion cells in sympathetic ganglia and the pelvic plexus were also found to contain dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), strongly suggesting that the NPY-IR cells are noradrenergic. NPY- and DBH-IR nerves had a roughly parallel occurrence in the heart, spleen, kidney, respiratory and urogenitary tracts, around blood vessels and within visceral smooth muscle. Considerably more NPY-IR than DBH-IR nerve fibres were seen in the gastrointestinal tract from the oesophagus to the anal sphincter. In addition, NPY-IR local ganglion cells were observed in the submucous and myentric plexuses. NPY-like immunoreactivity was also observed in the adrenal medulla of guinea-pig and cat. NPY thus seems to be a major peptide in the sympathetic nervous system, supporting its proposed role in sympathetic neurotransmission.

Animals↗

An ion exchange chromatography and radioimmunoassay procedure for measuring opioid peptides and substance P.

The measurements of peptides of the enkephalin, dynorphin and substance P systems is complicated by the number of possible precursor fragments and degradation products that might cross-react with the antisera. By using an ion-exchanger step before radioimmunoassay we can reduce the possibility that observed peptide levels are due to precursors or metabolites. The ion-exchanger method runs with good recovery and its main advantage is that many samples can be run in parallel. The recovery from the ion-exchanger was similar using two different homogenizing media, whereas the measured endogenous levels of [Met] and [Leu]enkephalin were 3-4 fold higher with 1M acetic acid than when a 1:1 MeOH/HCl mixture was used for tissue extraction.

Acetates↗

Electrophoresis of opioid peptides on columns with agarose suspension.

Opioid peptides have been fractionated by column electrophoresis in agarose suspension. The procedure provides a high resolution efficiency and compares favorably with high-performance liquid chromatography. Peptides were recovered from the column in 70% or higher yields when run in the femtomole to the nanomole range. By choosing different pHs it is possible to get complete resolution of a number of different endorphins. The electrophoreses were performed in volatile buffers, which are easily evaporated, and the residues are suitable for direct screening by radioreceptor- or radioimmunoassays. In combination with these assays the separation procedure makes it possible to detect and identify very low concentrations of endorphins in samples of biological origin.

Electrophoresis, Agar Gel↗

NADPH-diaphorase: a selective histochemical marker for striatal neurons containing both somatostatin- and avian pancreatic polypeptide (APP)-like immunoreactivities.

Certain neurons in the brain are specifically and intensely stained by a histochemical method which demonstrates nicotinamide adenine dinucleotide phosphate NADPH-diaphorase activity. The cell types containing this enzyme in certain areas of the rat forebrain were examined by combining NADPH-diaphorase histochemistry with the indirect immunofluorescence technique. Neurons containing somatostatin- or avian pancreatic polypeptide (APP)-like immunoreactivities were found throughout the forebrain including the striatum and neocortex. These two neuropeptides were also found to coexist in many telencephalic neurons. After photography, the sections processed for immunohistochemistry were stained for NADPH-diaphorase activity by a histochemical method. It was found that within the striatum all of the neurons that were selectively stained by this technique also contained both somatostatin- and APP-like immunoreactivities. Also in the neocortex NADPH-diaphorase was found only in those neurons displaying somatostatin- or APP-like immunoreactivity. In other brain regions such as the nucleus laterodorsalis tegmenti, NADPH-diaphorase-containing cells did not contain these neuropeptides. The results indicate that NADPH-diaphorase histochemistry provides a simple, reliable, histochemical method to demonstrate those striatal neurons in which somatostatin- and APP-like immunoreactivities coexist. The selective occurrence of this enzyme within these neurons may provide a useful target for pharmacological studies of these neuropeptide-containing cells.

Animals↗

Studies on the release by somatic stimulation from rat and cat spinal cord of active materials which displace dihydromorphine in an opiate-binding assay.

Using the spinal superfusion procedure, in anesthetized rats and cats, the presence of active factors which displace dihydromorphine in brain opiate binding studies, has been observed. Separation of this activity on a Sephadex G-10 column reveals the presence of two fractions which occur before (Fraction I) and after (Fraction II) the salt peak which account for over 70% of the observed dihydromorphine-displacing activity. The ratio of activity in Fraction II/Fraction I is 33 and 21, in the resting spinal perfusates of the rat and cat, respectively. High intensity, bilateral stimulation of the sciatic nerve in cats, results in a 30- and 5.4-fold increase in the levels of Fraction I and Fraction II, respectively, over pre-stimulation levels. In rat, bilateral stimulation of the hind paws, resulted in a frequency-dependent increase in the levels of Fraction I (1.9- and 3.2-fold at 5 and 50 Hz, respectively). Dynorphin 1-13 fragment elutes at least partly in Fraction I. With regard to Fraction II, the peak co-chromatographs with hexapeptide derivatives of enkephalin. Met- and Leu-enkephalin (Fraction III), elute off the column at a point where opiate receptor displacing activity is relatively small. Electrophoretic separation of Fraction I radioreceptor activity of alkaline and acid pH on agarose columns revealed two principle peaks which co-migrated with alpha-neoendorphin and dynorphin 1-13. Fraction II activity appeared primarily in a single peak which was isographic with enkephalin hexapeptides. Using radioimmunoassays, detectable levels of dynorphin and Met-enkephalin were observed and sciatic nerve stimulation resulted in significant increases. Neither column-coupled radioreceptor assays nor radioimmunoassays revealed the presence of beta-endorphin. The present experiments demonstrate the releasability by high intensity somatic stimulation of a variety of opioid peptides present in spinal terminals. Significantly, however, the majority of this activity appears to be found in fractions different from those of the pentapeptide enkephalins.

Animals↗

Characterization of electrophoretically separable endorphins in human CSF.

Opioid peptides have been purified from large pooled samples of human cerebrospinal fluid. The purification steps involved chromatography on Sephadex G-10 and electrophoresis in agarose suspension. The purified material was further characterized by HPLC and radioimmunoassay. All procedures were guided by a specific radioreceptor assay. The Sephadex G10 fractionation yielded receptor activity in two discrete fractions, Fraction I (FI) and Fraction II (FII). A second Sephadex run of FII gave a partial resolution of two components, one of which was larger (FIIA). Electrophoresis resolved these fractions into several components, most of which showed a more basic behaviour than the enkephalins. Thus, FI separated into at least 4 components and FIIB into two components while FIIA remained a single peak. These components appeared to migrate as distinct peaks and some of them also chromatographed on a HPLC-column as single components. Considering their behaviour in electrophoresis and on HPLC, two components are suggested to represent known endorphin structures. The predominant FII component (FIIA) was thus indistinguishable from Met-enkephalin-Lys6 in all chromatographic systems and one of the most basic FI components showed close similarity with dynorphin. Each of these components occurs at a higher concentration than Met- or Leu-enkephalin, dynorphin or beta-endorphin.

Chromatography, High Pressure Liquid↗

Immunocytochemical identification of polypeptide YY (PYY) cells in the human gastrointestinal tract.

Various parts of the human gastrointestinal tract were investigated immunocytochemically for the occurrence of polypeptide YY (PYY) and pancreatic polypeptide (PP). PYY-immunoreactive cells were observed in the lower part of the ileum, in the colon and in the rectum, and PP-immunoreactive cells were found in the colon and rectum. Both cell types were of the open type, i.e. they extended from the basal lamina to the gut lumen. PYY-immunoreactive cells were seen to emit cytoplasmic processes to the neighbouring goblet cells. This latter observation suggests that PYY cells may exert a paracrine action on the mucus-secreting goblet cells. Staining of consecutive thin plastic sections and staining of the same section simultaneously for two peptides showed that PYY-immunoreactivity did not occur in PP- or enteroglucagon-immunoreactive cells. On the ultrastructural level PYY-immunoreactivity was localized in basal granulated endocrine cells. These cells contained round or slightly oval electron dense granules with a mean diameter of 150 nm (range 100-300 nm).

Digestive System↗