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At least 775 records · Page 43Linked to original sources
PubMed1988

Evidence for release of copper in the brain: depolarization-induced release of newly taken-up 67copper.

The potential importance of copper (Cu) in neurosecretion can be inferred from the demonstration that extracellular Cu modulates the secretory function of peptidergic neurons (in vitro studies) and from the presence of high Cu concentrations in nerve terminals and secretory vesicles, primarily within the soluble matrix of the latter. We have previously hypothesized that vesicular Cu is released from neurons undergoing exocytosis and that such extracellular Cu plays an important modulatory role in the central nervous system. To test this Cu release hypothesis, rat hypothalami were incubated under in vitro conditions for 1 or 2 hr with 20 nM radiolabeled Cu (67Cu), and then 67Cu release was stimulated by a depolarizing concentration (60 mM) of K+. K+ markedly (P less than 0.001) stimulated 67Cu release in a Ca2+-dependent manner (stimulated release was 95 fmol/10 min/mg protein after 1 hr 67Cu loading and 160 after 2 hr). These amounts of released 67Cu account for about 10% of the total 67Cu taken up by the tissue. These results indicate that part of the 67Cu taken up by hypothalamic explants is directed into an intracellular compartment from where it can be released by a Ca2+-dependent mechanism, thus providing strong support to our hypothesis that release of copper is operative in situ in the brain.

Animals↗
PubMed1997

Parallel detection of Na,K-ATPase alpha subunit isoforms by pan-specific monoclonal mAb 9A7.

While emphasis has been placed upon those proteins which either mediate or respond to the rapid influx of calcium following depolarization, there has been little emphasis upon those proteins which aid in the reequilibration of the membrane potential. In an effort to identify presynaptic membrane proteins implicated in neurosecretion, monoclonal antibodies were screened against proteins which cosegregated with neuronal voltage-dependent calcium channels (VDCC) following immunoprecipitation. One monoclonal antibody (mAb 9A7) identified a 110-kDa protein. Micropeptide sequencing of (i) the mAb 9A7 immunoaffinity purified antigen and (ii) the 110-kDa protein present in the neuronal (N-type) VDCC preparation (McEnery et al., 1991, Proc. Natl. Acad. Sci. 88, 11095-11099) indicated identity with the alpha subunit(s) of the Na,K-ATPase. Further characterization by Western blotting, immunochemical localization, and immunoaffinity purification indicated that mAb 9A7 not only recognized the alpha3 isoform which is predominant in neuronal tissues but also identified the alpha1 and alpha2 isoforms. mAb 9A7 exhibited a wide cross-species reactivity and recognized human, rat, and mouse alpha subunit isoforms at an internal epitope. The pan-specificity of mAb 9A7 and the differential mobility of the alpha1 isoform relative to the alpha2 and alpha3 permitted parallel detection of multiple alpha isoforms. Western blot analysis of undifferentiated rat pheochromocytoma cell line (PC12) and human neuroblastoma (IMR32) cells indicated coexpression of the alpha1 and alpha3 isozymes. Upon differentiation of IMR32 cells by dibutrylyl-cAMP, a substantial increase in the alpha3 relative to the alpha1 isoform was observed. While the enrichment of total Na,K-ATPase may reflect the increased demand for ATP-dependent ion transport as IMR32 cells become more excitable, the specific increase in the alpha3 isoform suggests a unique role of this isoform during IMR32 cell differentiation.

Animals↗
PubMed2000

Erythropoietin inhibits calcium-induced neurotransmitter release from clonal neuronal cells.

Erythropoietin (EPO) and EPO receptor (EPO-R) are expressed in the brain but their neuronal functions are not yet clarified. The effects of EPO on neurosecretion were studied using clonal rat pheochromocytoma PC12 cells. EPO suppressed Ca(2+)-induced dopamine release from PC12 cells in a concentration- and time-dependent manner. Inhibition was also produced by an EPO mimetic peptide 1 (EMP1), a small synthetic peptide agonist of EPO-R, but not by its inactive analogue in which Cys residues were substituted with Ser. Inhibition was abolished by genistein but not by genistin. EPO and EMP1 induced autophosphorylation of Janus kinase 2 (JAK 2), a tyrosine kinase that associates with EPO-R, and dephosphorylation of GAP-43 in a tyrosine kinase-dependent fashion. These results suggest that EPO suppresses neurotransmitter release through activation of EPO-R linked to JAK2.

Animals↗
PubMed2001

Progesterone receptors as neuroendocrine integrators.

Intracellular progesterone receptors (PRs) are ligand-inducible transcription factors that mediate the majority of the effects of progesterone (P) on neuroendocrine functions. During the past decade, evidence has accumulated which suggest that PRs can also be activated independently of P, by signals propagated through membrane-bound receptors to the interior of cells. The activation of PRs by this type of "cross-talk" mechanism has been implicated in the physiological regulation of several important neuroendocrine processes, including estrous behavior and periovulatory hormone secretions. We review evidence that both ligand-dependent and ligand-independent activation of PRs occurs in central neurons and in anterior pituitary cells and that the convergence and summation of these signals at the PR serves to integrate neural and endocrine signals which direct several critically important neuroendocrine processes. An integrative function for PRs is reviewed in several physiological contexts, including the display of lordosis behavior in female rodents, the neurosecretion of gonadotropin-releasing hormone surges, secretion of preovulatory gonadotropin surges, and release of periovulatory follicle stimulating hormone surges. The weight of evidence indicates that cross talk at the intracellular PR is an essential component of the integrative mechanisms that direct each of these neuroendocrine events. The recurrence of PR's integrative actions in several different physiological contexts suggests that other intracellular steroid receptors similarly function as integrators of neural and endocrine signals in other neuroendocrine processes.

Animals↗
PubMed2000

Synaptobrevin 2 is palmitoylated in synaptic vesicles prepared from adult, but not from embryonic brain.

Neuronal SNARE-proteins such as synaptobrevin, SNAP 25, and synaptotagmin are key players during neurosecretion. So far palmitoylation of SNAP-25 and synaptotagmin 1 have been described in vivo. Here we have analyzed palmitoylation of the SNARE-proteins synaptobrevin 2 and synaptotagmin in vitro using synaptosomal and synaptic vesicle preparations from rat brain. Labeling of synaptic vesicles prepared from adult brain with [3H]palmitate revealed synaptobrevin 2 besides synaptotagmin 1 as major palmitoylated proteins. [3H]Palmitoylation of synaptobrevin 2 was resistant to chloroform/methanol extraction, but sensitive to reducing agents indicating a covalent fatty acid bond to cysteine residues. Palmitoylation of synaptobrevin 2 was also confirmed using endogenous synaptobrevin 2 present in PC-12 cells and synaptobrevin 2 expressed with a vacciniavirus system in Cos cells. In contrast to the situation seen with membrane preparations obtained from adult brain, synaptic vesicles prepared from embryonic rat brain did not support [3H]palmitoylation of synaptobrevin and synaptotagmin. These results suggest, that both synaptobrevin 2 and synaptotagmin were efficiently palmitoylated from mature synaptic vesicles. However, at least one component of the palmitoylation machinery is developmentally upregulated.

Age Factors↗
PubMed1983

Cytodifferentiation of the paraventricular nucleus in the chick embryo. A Golgi and electron-microscopic study.

The developmental changes in the cytoarchitecture of the hypothalamic paraventricular nucleus of the chick embryo were studied with particular emphasis on the differentiation of the magnocellular neurons. These cells can be distinguished from the parvocellular elements starting from stages 34--35 (Hamburger and Hamilton 1951) in Golgi-impregnated specimens. At the same stages, electron microscopy reveals dense-core granules, resembling the characteristic elementary granules of the neurosecretory material in the cytoplasm of the larger neurons. In addition, a few immature synapses were observed on these magnocellular perikarya. The present observations suggest that the early onset of neurosecretion in this area may be neurally regulated during early phases of development.

Animals↗
PubMed1988

Abundant GABAergic innervation of rat posterior pituitary revealed by inhibition of GABA-transaminase.

An antibody against gamma-aminobutyric acid (GABA) was used to identify GABAergic elements immunocytochemically in the rat posterior pituitary. In order to increase the intracellular concentration of GABA, rats were treated with the GABA-transaminase inhibitor gamma-vinyl-GABA (GVG). Light-microscopic observations of Vibratome and semithin sections revealed the presence of numerous immunoreactive nerve fibers throughout the neural lobe; the mean number and length of these fibers increased by 90% after GVG treatment. Electron microscopy demonstrated the immunostained axons to be of small diameter. The reaction product was confined to small vesicles. No immunostaining occurred in pituicytes. The richness of the GABAergic innervation of the neural lobe contrasts with previous reports using antibodies against glutamate decarboxylase and supports the idea that GABA participates in the presynaptic control of neurosecretion.

4-Aminobutyrate Transaminase↗
PubMed1976

Perivascular regions of the rat neural lobe.

Neural lobes and portions of occipital cortex from rats were examined electron microscopically following fixation in 4% tannic acid in 2.5% glutaraldehyde. The procedure allowed a clear demonstration of the perivascular space and intercellular spaces in both tissues. The perivascular spaces in the neurosecretory tissue was far more extensive than in the neural tissue and the role of this region in relation to the process of neurosecretion is discussed.

Animals↗
PubMed1979

ACTH-like immunoreactivity in two electronically coupled giant neurons in the pond snail Lymnaea stagnalis.

Two giant neurons (diameter 130 micron) were identified immunocytochemically by means of the unlabeled antibody enzyme technique with anti-ACTH 1-39 and 1-24 in the pond snail Lymnaea stagnalis. The cells are located in the visceral and the right parietal ganglion, respectively. They contain moderately electron dense elementary granules (diameter 150-160 nm). By means of the intracellular horseradish peroxidase injection technique it was shown that the cells send fibres into the neuropiles of various ganglia and into nerves. Synapses occur on the fine fibre branches in the neuropile. Synapse-like structures were found on the cell bodies and on the major fibres. The giant neurons are electrotonically coupled. With toluidine blue staining for small peptides it was demonstrated that in the central nervous system of the pond snail numerous peptidergic neurons occur in addition to those identified with the classical staining methods for neurosecretion.

Adrenocorticotropic Hormone↗
PubMed1980

Glycoprotein secretion in the hypothalamo-neurohypophyseal system of the rat.

Although the secretory products of the hypothalamo-neurohypophyseal system are not glycoproteins, synthesis and migration of these macromolecules occur within its secretory neurons. After being labeled with 3H-fucose in the Golgi apparatus, newly synthesized glycoproteins migrate to secretion granules, lysosomes and the plasma membrane of the secretory neurons, as demonstrated by quantitative electron-microscopic radioautography. Secretion granules bearing newly synthesized glycoproteins migrate to the pars nervosa, the labeling pattern of which was studied in rats killed from 4 h to 14 days after the isotope injection. Most of the silver grains were observed to overly the secretory axons. Labeling of pituicytes was negligible and the number of silver grains over the perivascular spaces was about 10% of the total at certain postinjection intervals. In the secretory axons, most of the silver grains over the different portions of the secretory axons changed with time. At the longer intervals, the percentage of silver grains increased over the nerve swellings (including Herring bodies) and decreased concomitantly in the undilated portions of the axons and in the nerve endings. This labeling pattern conforms with observations of the secretion products. Water deprivation increased the release of neurosecretion as well as glycoproteins from the pars nervosa. However, glycoproteins inside the Herring bodies were not easily releasible. There was a parallel decrease in the amount of secretion granules and 3H-fucose-labeled glycoproteins indicating that the glycoproteins are predominantly a constituent of the granule content. Some newly synthesized glycoproteins were probably also used in the renewal of the axonal membrane. The labeling of smooth vesicles in nerve endings was discussed. In conclusion, most of the glycoproteins synthesized in the perikarion of the hypothalmic secretory neurons migrate inside secretion graules along the axon to the pars nervosa where they are secreted.

Animals↗
PubMed1981

Fine structure of the cirri and a possible mechanism for their motility in stalkless crinoids (Echinodermata).

Crinoid cirri are jointed appendages that can slowly bend and straighten. The structures causing each cirrus to move have not been identified unequivocally by light microscopy; therefore, we examined them by electron microscopy. No muscle cells were found, but a probable contractile apparatus was demonstrated in the cytoplasm of epithelial cells lining the oral and aboral coeloms running the length of the cirrus. The presumed contractile apparatus is a bundle of 5 nm filaments oriented parallel to each other and to the long axis of the appendage. We have proposed that contractile shortening of the coelomic epithelia bends the cirrus in an aboral direction, since the fulcral articulations of the skeletal ossicles are oral to the contractile tissue; this active bending is presumably opposed by an elasticity of the oral ligaments, which seem to straighten the cirrus. It is possible that ligaments of the cirrus may undergo neurosecretion-mediated changes in consistency that could lock the appendage into a rigid state; however, active contraction by the ligaments appears unlikely.

Animals↗
PubMed1994

Diapause-dependent changes in prothoracicotropic hormone-producing neurons of the tobacco hornworm, Manduca sexta.

The prothoracicotropic hormone (PTTH), which stimulates ecdysteroid synthesis in the prothoracic glands, is produced, in the dorso-lateral protocerebrum of Manduca sexta, by paired peptidergic neurons, the lateral neurosecretory cell group III (L-NSC III). Our study revealed ultrastructural features of L-NSC III, identified by immunogold labeling, and compared developing and diapause states. In developing and early-diapause pupae, L-NSC III soma ultrastructure is similar and is characterized by numerous clusters of neurosecretory granules (NSG) and an extensive trophospongium formed by satellite-glial cells. However, as diapause progresses, the ultrastructure changes, with the NSG becoming concentrated into large clusters separated by highly organized rough endoplasmic reticulum. Most conspicuous is a substantial reduction in the number of Golgi complexes and the glial trophospongium, and the presence of stacked plasma membrane separating the glia and neuron somata. The deep-diapause soma also has abundant glycogen deposits and autophagic vacuoles. With diapause termination, this morphology reverts to the nondiapause ultrastructure within three days, i.e. just before PTTH release that evokes development to the adult. During PTTH release the abundance of NSG in the soma does not change, suggesting that NSG depletion in the perikarya is not a marker for neurosecretion by the L-NSC III.

Aging↗
PubMed1987

Dihydropyridine inhibition of neuronal calcium current and substance P release.

Dihydropyridine (DHP) calcium channel antagonists, which inhibit the slowly inactivating or L-type cardiac calcium (Ca) current, have been shown to be ineffective in blocking 45Ca influx and Ca-dependent secretion in a number of neuronal preparations. In the studies reported here, however, the antagonist DHP nifedipine inhibited both the L-type Ca current and potassium-evoked substance P (SP) release from embryonic chick dorsal root ganglion (DRG) neurons. These results suggest that, in DRG neurons, Ca entry through L-type channels is critical to the control of secretion. The inhibition of Ca current by nifedipine was both voltage and time-dependent, significant effects being observed only on currents evoked from relatively positive holding potentials maintained for several seconds. As expected from these results, nifedipine failed to inhibit L-type Ca current underlying the brief plateau phase of the action potential generated from the cell's normal resting potential; likewise, no significant effect of the drug was observed on action potential-stimulated SP release evoked by electrical field stimulation. The results of this work are discussed in terms of an assessment of the role of L-type Ca channels in neurosecretion.

Action Potentials↗
PubMed1988

Malignant peripheral neuroectodermal tumours of bone other than Askin's neoplasm: characterization of 14 new cases with immunohistochemistry and electron microscopy.

Peripheral neuroectodermal tumours (PNET) of bone are rare and mimic those seen in soft tissue (peripheral neuroepithelioma of soft tissue). Their differential diagnosis from Ewing's sarcoma (Es) is extremely difficult by optical means. Here we report 14 new cases of PNET of bone (other than Askin's neoplasm) located primarily in the limbs, pelvic girdle and scapula. Clinically and radiologically they displayed Ewing's sarcoma-like features: mean age was 14.4 years, male/female ratio being 3:11. Metastasis was present in 6 cases at diagnosis (5 with bone metastasis). Prognosis was poor; thirteen patients died; only one with a metatarsal located tumour is alive and free of disease. The mean survival rate was 25 months following diagnosis and treatment with radio- and multimodal chemotherapy. Histologically the 14 cases displayed Homer-Wright rosettes and pseudorosette-like structures, as well as a fibrillary background and lobular pattern. Immunohistochemistry revealed positivity in a number of neural markers when using paraffin-embedded material: NSE, B-2-microglobuline, HNK-1 (leu-7) and E-36 antibodies. At EM level the cell cytoplasms evidenced dense-core granules with neurosecretion, neurotubules and intermediate filaments like those seen in peripheral neuroepithelioma.

Adolescent↗
PubMed1993

Modulation of potassium evoked secretory function in rat cerebellar slices measured by real time monitoring: evidence of a possible role for methylfolate in cerebral tissue.

The real time dynamics of K+ evoked neurosecretion in cerebellar slices has been monitored electrochemically. In the presence of 5-methyltetrahydrofolate a statistically significant diminution in secretory response occurs. Agonists to probe the pharmacological basis for this indicate it is not due to voltage sensitive Ca2+ channel blockade, nor does it show any similarity of effect with kainate, whose receptor is a putative binding site for 5-methyltetrahydrofolate. The method is fully validated, although no account is taken of individual molecular species. High performance liquid chromatography combined with off line microbiological assay could only detect 5-methyltetrahydrofolate in cerebrospinal fluid. We therefore discuss our findings in relation to possible cerebral roles for cerebrospinal fluid 5-methyltetrahydrofolate in the context of both membrane and transmitter related interactions.

Animals↗
PubMed1990

Inhibitory effects of neuropeptide Y on sympathetic neurotransmission in the rabbit iris-ciliary body.

Neuropeptide Y (NPY, 1-300 nM) mediated a concentration-dependent inhibition of field stimulation-evoked [3H]norepinephrine (NE) overflow from the isolated, superfused rabbit iris-ciliary body. At equimolar concentrations (100 nM), the homologous neuropeptide peptide YY (PYY) mimicked the effects of NPY, whereas pancreatic polypeptide (PP) and the C-terminal fragment of NPY did not modify [3H]NE release. NPY-induced inhibition of [3H]NE release was unaffected by pretreatment of tissues with atropine (100 nM) plus yohimbine (100 nM) and was non-additive with the maximal prejunctional effects of carbamycholine or clonidine, indicating that NPY acts independently of prejunctional muscarinic or alpha 2-adrenergic receptor activity to reduce [3H]NE overflow. It is concluded that NPY is a specific, potent modulator of adrenergic neurosecretion in the rabbit iris-ciliary body. These findings confirm the role of NPY as a co-transmitter at ocular sympathetic neuroeffector junctions, either mimicking or augmenting the actions of endogenously released norepinephrine.

Animals↗
PubMed1991

Multifunctional features of a gastrodermal sensory cell in Hydra: three-dimensional study.

Computer-assisted, three-dimensional reconstructions of two gastrodermal sensory cells from transmission electron micrographs of serial sections of Hydra revealed a unipolar morphology with the nucleus near an apical cilium and a simple unbranched axon with a widened terminal. The sensory cells were similar in size and shape to a unipolar sensory cell isolated from macerated gastrodermis and examined with scanning electron microscopy. In thin sections, the cells were characterized by the presence of numerous dense-cored vesicles in the axon and its terminal. A few dense-cored vesicles were aligned at electron-dense synaptic foci in the axon terminal of the sensory cell, which formed an axo-axonal synapse with a nearby centrally located ganglion cell and a neuromuscular synapse with the basal myoneme of a digestive cell. The ganglion cell possessed a perikaryal cilium and a slender axon that extended adjacent to the sensory cell terminal, where it formed an en passant axo-axonal synapse in reciprocal arrangement with that of the sensory cell. In addition, the ganglion cell axon formed a neuromuscular synapse in sequence with the sensory cell axo-axonal synapse. The presence of a large number of neurosecretory-like granules, apical cilium and reciprocal interneuronal and neuromuscular synaptic loci suggests that this gastrodermal sensory cell, characterized ultrastructurally for the first time, represents a third type of multifunctional neuron in Hydra. Thus, Hydra may contain primitive stem-like neurons, which are sensory-motor and also function in both neurosecretion and neurotransmission.

Animals↗
PubMed1989

Psychoneuroendocrine research in depression. II. Hormonal responses to releasing hormones as a probe for hypothalamic-pituitary-endorgan dysfunction.

The rapid growth of fundamental research in neuroendocrinology includes advances in our understanding of the role of neurotransmitters in the control of hypophysiotropic neurons, the concept of neurosecretion, the portal circulation chemotransmitter hypothesis of anterior pituitary regulation, and the chemical structures of the hypophysiotropic hormones. These advances correspond to the emergence of psychoneurobiology, with the appreciation of the roles of neuropeptides, such as hypothalamic releasing and inhibiting hormones, their relevance to brain function and possible involvement in psychiatric disease, and their introduction into psychoneuroendocrinological studies. The subject of the present review is to summarize and integrate current knowledge of the neuroendocrinology of hypothalamic releasing and inhibiting hormones, to apply it to the understanding of the pathogenesis of depression, and to evaluate their relevance as psychoneuroendocrine research tools.

Corticotropin-Releasing Hormone↗