Dynorphin and Vasopressin: Common Localization in Magnocellular Neurons

Watson, S.J.; Akil, Huda; Fischli, Walter; Goldstein, Avram; Zimmerman, Earl A.; Nilaver, Gajanan; Griedanus, TB van wimersma

doi:10.1126/science.6121376

Cited by 423 publications

(137 citation statements)

References 28 publications

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“…We found a similar distribution for oxytocin in these tissues as has been reported by others (19,25). It has been reported that another opioid peptide, dynorphin, is present in vasopressin-containing magnocellular neurons (9,13). The dynorphins and neoendorphins arise from a precursor protein, prodynorphin, which does not contain the sequence of…”

Section: Discussionsupporting

confidence: 75%

“…The hypothalamus is also rich in opiate peptides (8)(9)(10)(11)(12)(13). We have shown here that proenkephalin and [Met]enkephalin IRs are present in oxytocin-containing magnocellular neurons of the bovine hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

“…Cell bodies containing 1-endorphin immunoreactivity (IR) are restricted to the arcuate nucleus (8). Dynorphin A and other peptides derived from prodynorphin have been found in magnocellular neurons (9)(10)(11)(12)(13). The presence in magnocellular neurons of peptides derived from proenkephalin is still uncertain.…”

mentioning

confidence: 99%

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Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons.

Vanderhaeghen¹,

Lotstra²,

Liston³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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The distribution of proenkephalin and [Met] Adsorbed antisera against oxytocin and vasopressin were generous gifts from F. Vandesande. Briefly, anti-vasopressin antiserum was adsorbed by treatment with oxytocin coupled to Sepharose 4B beads. Anti-oxytocin--antiserum was similarly treated with vasopressin-Sepharose 4B. Complete details on the preparation and specificity of these antisera have been reported (19).For the production of the anti-proenkephalin antiserum, a protein composed of the first 77-amino-acid residues of adrenal proenkephalin was purified from the adrenal medulla (16). The purified protein was injected into the popliteal lymph nodes of adult male Bourgogne rabbits. Antiserum obtained 2 wk after the third injection was found to be suitable for this study. Crossreactivity in a radioimmunoassay using this antiserum was less than 0.001% for the following peptides: [Met] 5139The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons.

Vanderhaeghen¹,

Lotstra²,

Liston³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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“…MNCs (Watson et al, 1982) and is found in the same secretory granules (Whitnall et al, 1983). It is therefore likely that both AVP and dynorphin are intra-dendritically cosecreted into the extracellular space of the magnocellular nuclei , possibly by somatic action potentials that backpropagate through the dendrites.…”

Section: Burst Terminationmentioning

confidence: 99%

Burst Initiation and Termination in Phasic Vasopressin Cells of the Rat Supraoptic Nucleus: A Combined Mathematical, Electrical, and Calcium Fluorescence Study

Roper¹,

Callaway²,

Armstrong³

2004

J. Neurosci.

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Vasopressin secreting neurons of the rat hypothalamus discharge lengthy, repeating bursts of action potentials in response to physiological stress. Although many electrical currents and calcium-dependent processes have been isolated and analyzed in these cells, their interactions are less well fathomed. In particular, the mechanism of how each burst is triggered, sustained, and terminated is poorly understood. We present a mathematical model for the bursting mechanism, and we support our model with new simultaneous electrical recording and calcium imaging data. We show that bursts can be initiated by spike-dependent calcium influx, and we propose that the resulting elevation of bulk calcium inhibits a persistent potassium current. This inhibition depolarizes the cell above threshold and so triggers regenerative spiking and further calcium influx. We present imaging data to show that bulk calcium reaches a plateau within the first few seconds of the burst, and our model indicates that this plateau occurs when calcium influx is balanced by efflux and uptake into stores. We conjecture that the burst is terminated by a slow, progressive desensitization to calcium of the potassium leak current. Finally, we propose that the opioid dynorphin, which is known to be secreted from the somatodendritic region and has been shown previously to regulate burst length and phasic activity in these cells, is the autocrine messenger for this desensitization.

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“…Immunocytochemical (8) and in situ hybridization studies (9) show that dynorphin (Dyn), which acts preferentially at kappa-receptors, is present in the SON and PVN. A moderate density of specific kappa-agonist binding sites has been localized in the SON by recent autoradiography study (10).…”

mentioning

confidence: 99%

Kappa‐Selective Opioid Receptor Agonists Leumorphin and Dynorphin Inhibit Supraoptic Neurons in Rat Hypothalamic Slice Preparations

Inenaga

Imura

Yanaihara

et al. 1990

J Neuroendocrinology

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To clarify the effects of opioid peptides, and in particular the effects of kappa-receptor agonists on the activity of supraoptic neurons, extracellular recordings were made from 71 spontaneously firing neurons in the rat hypothalamic slice preparation. Of 71 neurons, 28 showed a phasic firing pattern (phasic neurons: putative vasopressin neurons). The mean firing rate of phasic neurons was 2.6 spikesls (intraburst firing rate 5.4f2.2 spikesls). The mean firing rate of neurons classified as non-phasic neurons (putative oxytocin neurons) was 4.5 spikesls. Following bath application of leumorphin (LM) at lo-' M, which has potent opioid activity at kappareceptors, 17 (61%) of 28 phasic neurons were inhibited and 22 (51%) of 43 non-phasic neurons were inhibited. Excitation was observed in only one non-phasic neuron. The dose-dependence of the response to LM was tested in five supraoptic neurons. There was an inverse relationship between LM concentration and percent change in firing rate. The threshold concentration of LM was approximately M. The relatively selective kappa-receptor antagonist, MR-2266, completely blocked the LM-induced responses.Its effects were long-lasting and only partial recovery was observed 2 h after the application of MR-2266. Dynorphin had similar inhibitory effects on supraoptic neurons to those obtained with LM when tested on the same neurons. In another series of experiments the mu-receptor agonist morphine and the delta-receptor agonist [D-Ala, D-leu]-enkephalin (DADLE) were applied to 28 supraoptic neurons (12 phasic and 16 non-phasic neurons) at lo-' M and their actions compared directly with that of LM. Only two of 12 phasic neurons tested were inhibited by DADLE and none of five phasic neurons tested was inhibited by morphine, while eight of the 12 neurons tested were inhibited by LM. By contrast the non-phasic neurons tested were inhibited by application of each of the peptides; seven of 16 neurons tested were not only inhibited by LM, but also five of 11 neurons by DADLE and seven of 15 by morphine. The magnitude of the responses varied from cell to cell. These results suggest that LM acts at the same receptors as dynorphin, and that opioids acting preferentially at kappa-receptors inhibit both vasopressin and oxytocin neurons while delta-and mu-receptor agonists inhibit primarily oxytocin neurons.Neurosecretory cells in the supraoptic nucleus (SON) synthesize arginine vasopressin (AVP) and oxytocin (OXT) and release the peptides from the posterior pituitary into the systemic circulation. A number of reports suggest that opioid peptides may play an important role in the control of the release of the posterior pituitary hormones, acting directly on the neurosecretory cells in the hypothalamus (1, 2) as well as on the nerve terminals in the posterior pituitary (3, 4). The receptors for opioid peptides can be divided into at least three subtypes (i.e. mu-, delta-and kappa-receptors) ( 5 ) and there is already some evidence on the effects of mu-and delta-receptor agonists on the...

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Dynorphin and Vasopressin: Common Localization in Magnocellular Neurons

Cited by 423 publications

References 28 publications

Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons.

Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons.

Burst Initiation and Termination in Phasic Vasopressin Cells of the Rat Supraoptic Nucleus: A Combined Mathematical, Electrical, and Calcium Fluorescence Study

Kappa‐Selective Opioid Receptor Agonists Leumorphin and Dynorphin Inhibit Supraoptic Neurons in Rat Hypothalamic Slice Preparations

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