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L Terenius

Publications and source records attributed to L Terenius.

At least 19 recordsLinked to original sources
PubMed1992

A selective and extremely potent antagonist of the neurokinin-1 receptor.

Sendide [Tyr6,D-Phe7,D-His9]-substance P(6-11) has been examined by measurements of ligand binding to crude membrane fractions and by functional tests on the spinally mediated behavioral response. Sendide potently displaced [3H]-labeled substance P (SP) binding to mouse spinal cord membranes in a competitive manner. In vivo, sendide, intrathecally co-injected with SP, competitively antagonized SP-induced scratching, biting and licking. The behaviors elicited by physalaemin, septide and [Sar9, Met(O2)11]-SP were also reduced by co-administration of sendide. Large doses of sendide were needed to reduce the action of neurokinin A, D-septide, neurokinin B and eledoisin. The in vitro and in vivo pharmacological profile of sendide demonstrated that it is a selective and extremely potent antagonist of the neurokinin-1 receptor.

Amino Acid Sequence↗
PubMed1992

Presence of a dynorphin-like peptide in a restricted subpopulation of catecholaminergic neurons in rat nucleus tractus solitarii.

Immunofluorescence colocalization techniques were used to examine the extent of coexistence of the endogenous opioid peptide dynorphin with catecholamines and the related opioid peptide enkephalin within neurons of the rat medulla oblongata. Immunoreactivities for dynorphin and the catecholamine-synthesizing enzyme tyrosine hydroxylase were found to coexist within a limited subpopulation of A2 catecholamine cells, localized to the medial nucleus of the nucleus tractus solitarii. Colocalization of the two opioid peptides was found mainly within perikarya situated in the medial and ventrolateral nuclei of the nucleus tractus solitarii. Triple-labeling studies revealed only rare cases of catecholamine/dynorphin/enkephalin coexistence. These data demonstrate that dynorphin is present within a restricted subpopulation of catecholamine neurons in the dorsal medulla oblongata. In addition, the content of either of the opioids enkephalin or dynorphin appears to distinguish subsets of medullary catecholamine neurons.

Animals↗
PubMed1992

Reappearance of calcitonin gene-related peptide-like immunoreactivity in the dorsal horn in the long-term dorsal root transected rat.

Calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fibers in the rat dorsal horn superficial laminae vanish almost completely 3 weeks following unilateral dorsal rhizotomy. After a prolonged survival (20 weeks) of dorsal rhizotomy there is, however, a reappearance of CGRP-IR fibers in the corresponding laminae of the dorsal horn. The density of such IR fibres showed a clear gradient with the lowest number found in the midlesion region and an increase in density towards the neighboring, intact segments. In normal as well as lesioned rats, no neurons intrinsic to the dorsal horn contained detectable levels of CGRP-like immunoreactivity (LI). Furthermore, no cells could, by use of in situ hybridization, be demonstrated to contain detectable levels of mRNA encoding for CGRP in the dorsal horn. Based on these findings, we suggest that the CGRP-IR fibers observed following long-term survival of dorsal rhizotomy derive from proliferating collateral branches of primary afferents of neighboring intact segments.

Animals↗
PubMed1992

Isolation of a hemoglobin-derived opioid peptide from cerebrospinal fluid of patients with cerebrovascular bleedings.

The hemorphins are peptides with opioid activity, which are enzymatically released from hemoglobin. A decapeptide identical to the sequence 32-41 of the beta-, delta-, gamma- or epsilon-chains of hemoglobin has been isolated from human ventricular cerebrospinal fluid (CSF). The peptide, designated LVV-hemorphin-7, was recovered in relatively high amounts (115-300 pmol per ml) from samples of patients with cerebrovascular bleedings, but was not detectable in control CSF. Its identity with the hemoglobin fragment was confirmed by mass spectrometry and gas-phase sequencing.

Amino Acid Sequence↗
PubMed1992

Distribution of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem.

The distribution of enkephalin (ENK)-like immunoreactivity (LI) in spinal cord and medulla oblongata of cat and gray monkey (Macaca fascicularis) was studied by use of immunofluorescence and peroxidase antiperoxidase (PAP) techniques. Possible coexistence between ENK- and 5-hydroxytryptamine (5-HT)-LI was also analyzed with double labeling immunofluorescence. Furthermore, in situ hybridization was used to demonstrate cell bodies in the brain stem expressing mRNA encoding for ENK. ENK-immunoreactive (IR) axonal varicosities and fibers were demonstrated throughout the spinal cord gray matter, with the highest density in the superficial dorsal horn, the area around the central canal, the intermediolateral cell column, the sacral parasympathetic nucleus, and in Onuf's nucleus. In the monkey ventral horn, ENK-IR varicose fibers could in some cases be demonstrated in very close apposition to cell bodies. A low degree of co-localization between ENK- and 5-HT-LI was seen in the spinal cord of both species. Still, fibers containing both compounds could as a rule be demonstrated in every section studied. The highest degree of coexistence was encountered in the motor nucleus of the ventral horn. Six weeks after a low thoracic spinal cord transection a decreased staining for ENK-LI was demonstrated in the ventral horn motor nucleus, whereas other parts of the spinal cord appeared unaffected. In the brain stem of cats after colchicine treatment, ENK-LI was found in a majority of the 5-HT-IR cell bodies in the raphe nuclei (nucleus raphe magnus, pallidus and obscurus) and in the lateral reticular nucleus (rostroventrolateral reticular nucleus). In cat not pretreated with colchicine, a few weakly stained ENK-IR cell bodies could be found in the midline raphe nuclei and in the lateral reticular nucleus with the PAP technique. In the monkey brain stem without colchicine treatment, using the PAP technique, heavily stained ENK-IR cell bodies could be seen in the lateral reticular nucleus whereas, as in the cat, only a few, weakly stained ENK-IR cell bodies could be seen in the midline raphe nuclei. Using in situ hybridization technique, ENK mRNA expressing cells were demonstrated in the lateral reticular nucleus while no convincing mRNA signal could be found over cell bodies in the raphe nuclei. It is concluded that part of the ENKergic innervation of the cord in both species derives from supraspinal or suprasegmental levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Substance P, thyrotropin-releasing hormone, and monoamine metabolites in cerebrospinal fluid in sleep apnea patients.

The cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone (TRH), substance P (SP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were measured in 15 consecutive patients with the sleep apnea syndrome (SAS) and in healthy control subjects. Second measurements were performed 6 months after surgical treatment in 10 of the patients. The mean (+/- SD) concentration of TRH-like immunoreactive material (TRH-LIM) (pg/ml) did not differ significantly between patients with SAS (8.1 +/- 2.8) and control subjects (7.5 +/- 2.2). However, postoperatively, this concentration was increased in the six clinically cured patients with SAS, from 6.9 +/- 2.7 to 9.4 +/- 1.6 (p less than 0.03). Substance P-like immunoreactive material (SP-LIM) was higher in untreated patients with SAS than in control subjects: 19.2 +/- 6.7 versus 14.4 +/- 4.2 fmol/ml (p less than 0.02), and the level remained high after operation in the group treated surgically. The HVA, 5-HIAA, and MHPG concentrations were similar in patients with SAS and control subjects, and no consistent changes were found postoperatively. The CSF deviations in TRH-LIM and SP-LIM concentrations in the patients may reflect a primary central nervous system defect or they may be secondary to intermittent nocturnal hypoxia, progressive hypercapnia, and/or sleep fragmentation. In this sense, both these systems may be markers of SAS-SP as a "trait" marker and TRH as an indicator of the current state.

Adult↗
PubMed1991

Calcitonin gene-related peptide in monkey spinal cord and medulla oblongata.

The distribution of calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fibers and cell bodies was studied in the spinal cord and the medulla oblongata of the grey monkey (Macaca fascicularis) using peroxidase-antiperoxidase (PAP) immunohistochemistry. At all levels of the spinal cord many CGRP-IR motoneurons and fibers were seen in the motor nuclei. In the medulla, CGRP-IR cell bodies were encountered in nucleus raphe obscurus, nucleus raphe pallidus and nucleus raphe magnus, nucleus reticularis lateralis as well as in the area dorsal to the inferior olive. Bulbar motoneurons were much more intensely stained than spinal cord motoneurons, indicating higher levels of CGRP-like immunoreactivity (LI) at the medullary level. The concentration of CGRP-LI measured by radioimmunoassay showed higher levels in the dorsal quadrants as compared to the ventral quadrants, but the dorsal/ventral ratio was lower than has previously been reported from the rat. The present results demonstrate that using the PAP technique CGRP-LI can be visualized in a larger number of spinal cord motoneurons of the monkey than earlier revealed by immunofluorescence. Moreover, the finding supports the view that the CGRP-IR nerve endings in the spinal motor nuclei originate from cell bodies in the medullary raphe nuclei.

Animals↗
PubMed1991

[Molecular neurobiological research in the fight against drug abuse].

Molecular biology has a strong impact on current research into drug and alcohol dependence. Spectacular recent results include the cloning of a cannabinoid receptor, nicotine receptors in the CNS and the targets of amphetamine and cocaine action, catecholamine transporters. Alcohol has been found to interact with the GABAA and NMDA (glutamate) receptors at concentrations reached with social alcohol use. The interactions of opiates and other drugs of abuse with the endogenous opioid peptides have been studied at several levels; it is a general finding that precursor gene transcription is suppressed. Although much less is known about the molecular consequences of chronic addictive drug usage, a functional deficit in opioid systems has been described. A general addiction mechanism may have similarities with memory storage mechanisms which are currently being studied with molecular probes.

Alcohol Dehydrogenase↗
PubMed1991

Isolation and characterization of a hemoglobin-derived opioid peptide from the human pituitary gland.

An opioid nonapeptide was isolated from fresh frozen human pituitaries. Its primary structure (Leu-Val-Tyr-Pro-Trp-Thr-Gln-Arg) was identical to fragment 32-40 of the beta-, delta-, gamma- and epsilon-chains of human hemoglobin. A larger peptide of about 4.5 kDa, which generated a fragment containing the nonapeptide on trypsin digestion, showed an amino acid composition similar to fragment 1-41 of the beta-chain of human hemoglobin. The nonapeptide interacted with mu-opioid receptors in rat brain homogenates using [3H]-(D-Ala2, MePhe3, Gly-ol5)-enkephalin and with sigma-receptors using (+)-[3H]-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine, respectively. The affinities for mu-opioid receptors were in the same range as those observed for the structurally related beta-casomorphins. However, the isolated peptide showed markedly higher affinity at sigma-binding sites when compared to the beta-casomorphins or other opioid peptides. The opioid potency of this peptide as determined in the guinea-pig ileum myenteric plexus muscle preparation, was significant but less than that observed for the beta-casomorphins.

Amino Acid Sequence↗
PubMed1991

Expression of preprodynorphin in human small cell lung carcinoma cell lines.

The expression of preprodynorphin has been studied using the Northern blot technique. Ten human cell lines, six small cell lung carcinoma (SCLC), one large cell carcinoma (LCC), two neuroblastoma and one lymphoblast-like cell line, were screened with a preprodynorphin cRNA-probe. Tryptic digestion followed by radioimmunoassay for Leu-enkephalin-Arg6 was used to detect possible translation of the preprodynorphin transcript. Of the ten cell lines investigated we found that all expressed preprodynorphin-mRNA to various degrees, and that this transcript is also translated. Two of the cell lines, neuroblastoma SK-N-MC and SCLC H69, also expressed preproenkephalin-mRNA. This set of cell lines provides a useful model of human origin in which the regulation of the preprodynorphin gene and the posttranslational processing of its products can be studied and compared.

Blotting, Northern↗
PubMed1991

Sequence similarity between opioid peptide precursors and DNA-binding proteins.

The opioid peptide precursors, preprodynorphin and preproenkephalin show structure similarity with a transcription factor, hunchback and the putative helix-loop-helix DNA-binding proteins, lil-1, tal and twist. Segments with similarity contain the three enkephalin sequences in preprodynorphin and one in preproenkephalin which are present within heptapeptide repeats characteristic of an alpha-helical coiled-coil structure distinctive of an amphipathic helix-loop-helix DNA-binding motif. Hunchback and the opioid prohormones also have cystein-rich regions characteristic of zinc-finger domains in common.

Amino Acid Sequence↗
PubMed1991

Immunohistochemical study of cholecystokinin peptide in rat spinal motoneurons.

With the aid of indirect immunofluorescence histochemistry and sequence specific antibodies a possible localization of cholecystokinin (CCK) peptide in spinal motoneurons has been analyzed. To increase peptide levels, the sciatic nerve was ligated, and the area around the ligation was studied 24 hours later. For comparison, antisera raised against calcitonin gene-related peptide (CGRP) and substance P were employed. With CCK specific antisera (directed to the N-terminal portion of CCK-8 or the midportion of CCK-33) accumulation of peptide-like immunoreactivity (LI) was observed in large, dilated axonal swellings proximal to, but at some distance from, the ligature. Such accumulations were also observed with C-terminally directed CCK antiserum, but in addition numerous axons of smaller diameter extending up to the ligation contained this type of immunoreactivity. The latter antiserum is thought to cross-react with CGRP. In fact, this staining pattern was indistinguishable from the one seen after incubation with CGRP antiserum. In contrast substance P-LI could not be seen in the larger dilated axons but only in large numbers of thinner fibers close to the ligation. Double staining experiments revealed that the large dilations contained both CGRP- and CCK-specific LI. Distal to the ligation CGRP- and substance P- but no specific CCK-LI could be observed. The present findings support the view that CCK mRNA in spinal motoneurons is translated into CCK peptide, at least after axotomy, and that the peptide is transported into the motoneuron axon. However, compared to CGRP the CCK levels are presumably low, and the functional role of CCK peptide in motoneurons remains to be established.

Animals↗
PubMed1991

Levels of dynorphin peptides, substance P and CGRP in the spinal cord after subchronic administration of morphine in the rat.

Rats were rendered dependent on morphine by repeated injections of morphine, in increasing doses for 14 days and sacrificed. Levels of peptides in the dorsal spinal cord and dorsal root ganglia were analyzed in rats decapitated 2 hr, 24 hr (acute abstinent) or 7 days (late abstinent) respectively, after the last injection of drug. Dynorphin A was significantly decreased in rats abstinent for 24 hr, while dynorphin B remained unaffected. Substance P and CGRP, both putative transmitters in nociceptive primary afferent neurones, and partly existing together in the same neurone, were affected differently. Significantly less substance P but unchanged levels of CGRP were detected in rats abstinent for 24 hr, while on the other hand, CGRP but not levels of substance P, were increased 2 hr after the final injection. In dorsal root ganglia, levels of substance P were lower at 2 hr, while levels of CGRP were unaffected. In late (7 days) abstinence, no effect of opiate on any peptide was detected.

Animals↗
PubMed1991

Effect of low- and high-frequency TENS on Met-enkephalin-Arg-Phe and dynorphin A immunoreactivity in human lumbar CSF.

Transcutaneous nerve stimulation (TENS) treatment was given for 30 min to 37 patients divided into 3 groups of 10 patients and 1 group of 7 patients. Two groups received low-frequency (2 Hz) and the other 2 groups high-frequency (100 Hz) stimulation. A diagnostic lumbar cerebrospinal fluid (CSF) sample was obtained immediately before and after stimulation. The CSF samples were subjected to analysis of immunoreactive (ir) opioid peptides, Met-enkephalin-Arg-Phe (MEAP) from preproenkephalin and dynorphin A (Dyn A) from preprodynorphin, respectively. Low frequency TENS applied on the hand and the leg resulted in a marked increase (367%, P less than 0.05) of ir-MEAP but not ir-Dyn A, whereas high-frequency (100 Hz) TENS produced a 49% increase in ir-Dyn A (P less than 0.01) but not ir-MEAP. This is the first report in humans that 2 Hz and 100 Hz peripheral stimulation induces differential release of peptides from preproenkephalin and preprodynorphin, respectively.

Adult↗
PubMed1991

Molecular heterogeneity of angiotensin converting enzyme in human cerebrospinal fluid.

Three different molecular forms of angiotensin converting enzyme (ACE) (approximately Mr 150,000, 80,000 and 40,000, respectively), have been recovered from human cerebrospinal fluid. All three enzymes were inhibited by captopril and enalapril and their activity was potentiated by chloride ions. They were capable of degrading Leu-enkephalin-Arg6 and substance -P, but gave no conversion of neurokinin A. In all these aspects, the CSF enzymes were identical with the human pulmonary enzyme. The Mr 40,000 form of ACE is the smallest active form of the enzyme hitherto reported and is likely to represent a fragment of the C-terminal part of native ACE, where its active center is located.

Amino Acid Sequence↗