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Biomedical subjects

B Scharrer

Publications and source records attributed to B Scharrer.

At least 19 recordsLinked to original sources
PubMed1994

Microglia in invertebrate ganglia.

The results of this study lend strong support to the concept of the existence in insects and molluscs of a distinctive class of neuroglial cells comparable to vertebrate microglia. The evidence presented is as valid as that used in reference to the separate status of vertebrate microglia--i.e., the demonstration of a close structural and functional relationship of these cells with cells of the immune system. As in vertebrates, the excision of ganglia from three invertebrate species (the molluscs Planorbarius corneus and Mytilus edulis and the insect Leucophaea maderae) and their maintenance in incubation media led to an exodus of small cells and their accumulation in the culture dish. During this process, they underwent conformational changes from stellate to rounded, and then to more or less ameboid, comparable to those indicative of the process of activation in the animals' immunocytes. Functional characteristics which these translocated microglia-like cells share with immunocytes are motility, phagocytotic activity, and adherence to the culture dish. Furthermore, the two cells have certain biochemical features in common--e.g., the presence of certain cytokines and (at least in Planorbarius) that of corticotropin. An additional phenomenon of particular interest for the classification of microglial elements is their response to morphine. At 10(-6) M, this drug decreases not only the number of cells emerging from the excised ganglia but also the degree of their transformation to the "active" ameboid form. This dose-dependent and naloxone-sensitive effect of morphine on microglial cells parallels that on activated immunocytes of the same species. Corresponding results demonstrating an inhibitory effect of morphine on mobilized microglial cells of the frog Rana pipiens indicate that this relationship between the two cell types under consideration also exists in vertebrates. Binding and displacement experiments with membrane homogenates of microglial cells as well as immunocytes of Mytilus have shown that the effects of morphine on both cell types are mediated by the same special opiate receptor (mu 3).

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PubMed1993

Opiate-like substances in an invertebrate, an opiate receptor on invertebrate and human immunocytes, and a role in immunosuppression.

The presence of morphine-like and codeine-like substances was demonstrated in the pedal ganglia, hemolymph, and mantle tissues of the mollusc Mytilus edulis. The pharmacological activities of the endogenous morphine-like material resemble those of authentic morphine. Both substances were found to counteract, in a dose-dependent manner, the stimulatory effect of tumor necrosis factor alpha or interleukin 1 alpha on human monocytes and Mytilus immunocytes, when added simultaneously to the incubation medium. The immunosuppressive effect of this opiate material expresses itself in a lowering of chemotactic activity, cellular velocity, and adherence. Codeine mimics the activity of authentic morphine, but only at much higher concentrations. Specific high-affinity receptor sites (mu 3) for morphine have been identified on human monocytes and Mytilus immunocytes. In Mytilus recovering from experimentally induced stress, the return of "altered" immunocytes to a more inactive state appears to be due to a significant rise in the content of morphine-like material in the pedal ganglia and hemolymph at this time. Thus, morphine may have a role in calming or terminating the state of immune alertness.

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PubMed1992

[D-Ala2]deltorphin I binding and pharmacological evidence for a special subtype of delta opioid receptor on human and invertebrate immune cells.

The effects of the opioid neuropeptide [D-Ala2]deltorphin I, isolated from amphibian skin, on immunoregulatory activities were studied in representatives of vertebrates and invertebrates. The high potency of this compound parallels that of [Met]enkephalin, which was previously demonstrated in vertebrate plasma and invertebrate hemolymph. The addition of [D-Ala2]deltorphin I at 10(-11) M to human granulocytes or immunocytes of the mollusc Mytilus edulis resulted in cellular adherence and conformational changes indicative of cellular activation. This value is in line with the concentrations obtained with [Met]enkephalin, tested in the presence of the specific neutral endopeptidase 24.11 inhibitor phosphoramidon, and this opioid's synthetic analog [D-Ala2, Met5]enkephalin which, like [D-Ala2]deltorphin I, is resistant to proteolytic degradation. Both ligands appear to be acting on the same population of immunocytes. The same relationship was estimated to exist in the insect Leucophaea maderae, in which the high viscosity of the hemolymph makes the quantification of reactive cells more difficult than in Mytilus. In addition, [D-Ala2]deltorphin I is as potent as beta-endorphin in affecting the proliferation of lymphocytes in response to mitogen. Saturation experiments with unlabeled ligands and the radioligands [3H][D-Ala2]deltorphin I and [3H][D-Ala2,Met5]enkephalinamide revealed the presence of two high-affinity binding sites on human granulocytes, one sensitive to the nonequilibrium delta opioid antagonist [D-Ala2,Leu5,Cys6]enkephalinamide and the other relatively insensitive. The results obtained with [D-Ala2]deltorphin I support the view that the special role played by endogenous [Met]enkephalin in immunobiological activities of vertebrates and invertebrates is mediated by a special subtype of delta opioid receptor.

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PubMed1991

A possible immunoregulatory function for [Met]-enkephalin-Arg6-Phe7 involving human and invertebrate granulocytes.

Opioid peptides and their analogs have been shown to stimulate adherence, conformational changes and locomotory activity in human as well as invertebrate granulocytes. The present study demonstrates that [Met]-enkephalin-Arg6-Phe7, an opioid substance thus far not included in these immunological tests, exhibits stimulatory effects comparable to those of [Met]-enkephalin in this regard. Furthermore, since neutral endopeptidase 24.11 (enkephalinase; CD10/NEP) exists in invertebrate immunocyte membranes, we demonstrate that its specific inhibitor, phosphoramidon, potentiates the effects of the heptapeptide in inducing conformational change in both human and invertebrate granulocytes. Additionally, the major metabolic products of NEP activity, Phe-Met-Arg-Phe and Tyr-Gly-Gly, appear to be potent antagonists of this enzyme activity, especially the tetrapeptide. The effects of heptapeptide stimulation showed a major difference between vertebrate and invertebrate immunocytes with respect to their time course, namely, the speed of their onset. [Met]-enkephalin-Arg6-Phe7 markedly stimulated the locomotory activity of these cells which becomes most noticeable within 15-45 min for Mytilus cells and in a 5-15 min period for human cells. It also enhanced the mobility and velocity of the responsive human (5 microns/min) and invertebrate cells (2.1 microns/min).

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PubMed1990

Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11.

The antigen CD10 (common acute lymphoblastic leukaemia antigen), which is the zinc metalloprotease, neutral endopeptidase 24.11 (also known as NEP or 'enkephalinase'), is expressed by acute lymphoblastic leukaemias, normal lymphoid progenitors, mature polymorphonuclear leukocytes and certain nonhaematopoietic cells. CD10/NEP hydrolyses several naturally occurring peptides, including the endogenous opioid pentapeptides Met- and Leu-enkephalin. In invertebrate organisms such as the mollusc Mytilus edulis, Met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration and aggregation of haemocytes. We report here that a structure related to CD10/NEP is expressed by M. edulis haemocytes and that abrogation of CD10/NEP enzymatic activity reduces the amount of Met-enkephalin required for haemocyte activation by five orders of magnitude. Similar results are obtained with CD10+ human polymorphonuclear leukocytes, indicating that CD10/NEP related structures regulate enkephalin-mediated inflammatory responses in organisms whose ancestors diverged approximately 500 million years ago.

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PubMed1990

Immunocytochemical localization and immunochemical characterization of an insulin-related peptide in the insect Leucophaea maderae.

Immunocytochemical tests with eight monoclonal antibodies against either bovine or human insulin and seven polyclonal antibodies against bovine insulin were carried out to determine the presence of insulin-like neuropeptides in the brain and affiliated neuroendocrine structures of the insect Leucophaea maderae. Reaction products identified in the brain, subesophageal ganglion, and corpus cardiacum-corpus allatum complex indicate the presence of materials resembling mammalian insulins in its antigenic properties. The immunostaining observed with monoclonal antibodies appears to indicate the occurrence of an insulin-related peptide that shows sequential similarities with parts of both the A- and B-chains of mammalian insulin molecules. These suppositions are supported by the results of dot-blot and two-site time-resolved immunofluorometric assay (TRI-IFMA) screenings of fractions of Leucophaea tissue extracts obtained by chromatography. The polyclonal antibodies yielded reaction products in some of the same areas and in additional parts of the neuroendocrine system not visualized by the monoclonal antibodies. Immunoreaction was observed in the following areas: the pars intercerebralis of the protocerebrum, the nervi corporis cardiaci I transporting insulin-like material to the corpus cardiacum, the dorsolateral protocerebral area and the optic lobes, the deutocerebrum, the tritocerebrum, and the subesophageal ganglion. In addition, smaller cell bodies with immunoreactive deposits occur at the border between proto- and deuto-cerebrum, and in the central area of the protocerebrum. The distribution of reactive material in the corpus cardiacum-corpus allatum complex after use of both groups of antibodies was the same.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1990

A neuroimmunoregulatory-like mechanism responding to stress in the marine bivalve Mytilus edulis.

Mytilus edulis has been the subject of recent studies to determine whether the relationship between the immune and nervous systems seen in vertebrates also exists in invertebrates. In the present study the effects of experimentally induced "stressful" stimuli on immunoactive hemocytes were studied in this mollusc. This subpopulation of invertebrate blood cells, resembling vertebrate granulocytes, has been previously shown to produce and react to opioid peptides. Their activation, like that of vertebrate immunocytes, expresses itself in distinctive conformational changes preceding cellular mobilization. The cellular response to "stress" observed is the same as that to the administration of exogenous mammalian opioid peptides. This strongly suggests that under the conditions of stressful stimuli, the immune/defense system can be altered by endogenous neuropeptides. The involvement of opioids in neuroimmunoregulatory phenomena appears to have a long evolutionary history.

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PubMed1990

Interaction of immunoactive monokines (interleukin 1 and tumor necrosis factor) in the bivalve mollusc Mytilus edulis.

Mytilus edulis has been the subject of recent studies to determine whether the relationship between the immune and neuroendocrine systems seen in vertebrates also exists in invertebrates. The effects of mammalian monokines were studied in Mytilus immunocytes previously shown to produce and react to opioid peptides. These invertebrate cells respond to interleukin 1 (IL-1) and tumor necrosis factor (TNF), both in vitro and in vivo, in a manner similar to that of human granulocytes. As in the mammalian monokine network, the effect of IL-1 on the immunocytes is brought about, at least in part, by its stimulatory effect on the formation of TNF. In addition, the presence of immunoreactive IL-1 and TNF in Mytilus hemolymph was demonstrated.

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PubMed1989

Stimulatory effects of opioid neuropeptides on locomotory activity and conformational changes in invertebrate and human immunocytes: evidence for a subtype of delta receptor.

The presence of opioid neuropeptides was shown to stimulate conformational changes and locomotory activity in immunocytes of two representatives of invertebrates as well as in human leukocytes. Cells were examined by use of phase-contrast and Nomarski optics coupled with a Zeiss Axiophot microscope, and of the Zeiss Videoplan/Vidas Image Analysis system. Immunocompetent blood cells, activated by exogenous opioids or stressful stimuli presumed to engage endogenous opioids, showed flattening, elongation, and formation of pseudopodia. In the mollusc Mytilus edulis, ameboid movements resulted in the formation of cell clusters, an activity not observed in untreated controls, or in immunocytes simultaneously exposed to opioid and naloxone. Tests with nine immunoreactive substances revealed immunocyte stimulation by delta, mu-, kappa-, and epsilon(?)-selective ligands. One of these, [D-Ala2,D-Met5]enkephalinamide (DAMA), active at a concentration of 10 pM, proved to be considerably more effective than the rest. The high pharmacological potency of DAMA, observed in both human and invertebrate immunocytes, sets this opioid apart from the closely related [D-Ala2,D-Leu5]enkephalin, a discrepancy not occurring in the mammalian nervous system. This suggests a specific function for [Met]enkephalin in immunoregulation, mediated perhaps by a special subtype of delta receptor.

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PubMed1989

Evidence for the involvement of opioid neuropeptides in the adherence and migration of immunocompetent invertebrate hemocytes.

Evidence for the participation of opioid neuropeptides in immunoregulatory activities, especially cellular adherence and migration, has been obtained in representatives of two phyla of invertebrates, the mollusc Mytilus edulis and the insect Leucophaea maderae. The injection of a synthetic analog of [Met]enkephalin [( D-Ala2,Met5]enkephalinamide, DAMA; 10(-6) M) had a stimulatory, naloxone-reversible effect on the directed migration of immunocompetent hemocytes. Incubation of hemolymph in the presence of exogenous or endogenous opioid material significantly enhanced the adherence of hemocytes on albumin-coated slides as demonstrated by use of indirect Zeiss-Zonax reflectance computer analysis. Conversely, hemocyte adherence was markedly reduced by the addition of naloxone (10(-8) M) to the incubation medium, either alone or in combination with DAMA. The antagonistic effects of naloxone on the stimulatory activities of opioids indicate that, like those previously reported in mammals, they are receptor-mediated. The presence of an endogenous [Met]enkephalin-like material was demonstrated in cell-free hemolymph as well as sequestered hemocytes by use of high-pressure liquid chromatography and radioimmunoassay. These results demonstrate that the capacity of immunocytes to release and respond to opioid neuropeptide messengers is not restricted to mammalian organisms but was developed early in the course of evolution.

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PubMed1988

Diversity of prolactin systems in the insect Leucophaea maderae: use of antiserum polyclonality for immunocytochemical detection of neuropeptide heterogeneity.

The presence of prolactin-like neuropeptides was demonstrated immunocytochemically in the brain and affiliated neuroendocrine structures of the insect Leucophaea maderae. Use of the unlabelled peroxidase-antiperoxidase method of Sternberger revealed a rather widespread and differential distribution of reaction products resembling human (hPRL) and ovine (oPRL) prolactin. Tests with antirat PRL antibody were negative. The specificity of the antibodies used was established by liquid-phase absorptions and confirmed in tissue control systems. In L. maderae, anti-oPRL identifies part of an oPRL-like molecule different from human and rat PRL. Anti-hPRL reveals part of a human and ovine PRL-like molecule different from rat prolactin. These results indicate the occurrence, in the nervous tissue of one insect species, of at least two types of prolactin-like molecules.

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PubMed1988

Opioid mechanisms in insects, with special attention to Leucophaea maderae.

1. This review article provides information on the evolutionary history of neuroendocrine and related regulatory mechanisms. It focuses on the presence, diverse roles, and modes of operation of one class of neuropeptides, the endogenous opioids, in insects. 2. Opioid peptides, closely resembling those of vertebrates, have been identified in the brain and related neuroendocrine structures by means of immunocytochemistry and high-pressure liquid chromatography. 3. The demonstration of naloxone-sensitive, high-affinity binding sites for Met-enkephalin-like neuropeptides in the brain and digestive tract of Leucophaea deserves special attention because it provides new insights into the functional significance of opiate receptors paralleling those known in vertebrates. 4. Possible roles of receptor-mediated opioid systems in the insects discussed are regulation of the cyclicity of the female reproductive system, maintenance of normal midgut function mediated by the recurrent nerve, and locomotor activity.

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PubMed1987

Gastrin/CCK-like immunoreactivity in the corpus cardiacum-corpus allatum complex of the cockroach Leucophaea maderae.

By use of immunocytochemistry, a gastrin/CCK-like material has been demonstrated in the corpus cardiacum-corpus allatum complex of the cockroach Leucophaea maderae. Reactivity toward gastrin and CCK with region-specific antisera suggests that the gastrin/CCK-like peptide of this insect contains the COOH-terminal tetrapeptide sequence which is common to gastrin and CCK, and that the material is more gastrin-like than CCK-like. The results indicate that, like other neuropeptides, the gastrin/CCK peptide family appeared early in evolution within neuronal elements, and that the COOH-terminal region of gastrin has been conserved during phylogeny.

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PubMed1982

Demonstration, characterization and localization of opioid binding sites in the midgut of the insect Leucophaea maderae (Blattaria).

The demonstration in the midgut of the insect Leucophaea of specific high affinity binding sites for a synthetic opioid represents the first report on neuropeptide binding in the digestive system of an invertebrate. Binding of the enkephalin analog DAMA (D-Ala2, Met5-enkephalinamide) is monophasic, saturable with respect to the concentration of the radioligand used, and stereospecific. Binding of the opiate antagonist naloxone to midgut homogenates is also monophasic, saturable, and stereospecific. The binding site density for DAMA is reduced by sodium and increased by manganese. By contrast, binding of naloxone is enhanced by sodium and unaffected by manganese. Lithium is equipotent with sodium in altering these values. Prolonged exposure of the organ to naloxone increases its binding capacity for DAMA. In midguts deprived of their autonomic innervation by severance of the recurrent nerve the binding capacity for the synthetic opioid is lower than in controls. Also, such 'denervated' organs are no longer affected by prolonged naloxone treatment. Results of tests for the presence in the midgut of non-peptidergic neurotransmitters (dopamine, norepinephrine) possibly operating in response to enkephalinergic signals, have thus far been negative. The results strongly suggest the existence in the digestive tract of this invertebrate of opioid receptors comparable to those in analogous mammalian systems.

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