Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dynorphin is found mainly in the particulate fraction of rat pituitary gland and hypothalamus homogenates. Dynorphin-like immunoreactivity (DYN-LI) from neurointermediate lobe (NIL) homogenates migrates at the same rate as vasopressin-like immunoreactivity (AVP-LI), in sucrose density gradients, whereas DYN-LI from the hypothalamus appears to migrate principally in a less dense region of the gradient. This suggests that dynorphin and vasopressin from pituitary are present in organelles of similar size and density, while the bulk of the dynorphin in the hypothalamus appears to be stored in a different subcellular organelle. Anterior lobe (AL) dynorphin appears to migrate in two separate bands on density gradients: the less dense band (slower) migrates at a similar rate to that of dynorphin and vasopressin from NIL. When alpha-neo-endorphin was measured in sucrose gradients of NIL and hypothalamus, it was found to co-migrate with DYN-LI.
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PMID:Subcellular localization of immunoreactive dynorphin and vasopressin in rat pituitary and hypothalamus. 613 Apr 35

Dynorphin (1-17), and to a lesser extent, beta-endorphin and [Leu]enkephalin (10(-6) M each) decreased the spontaneous release of vasopressin (VP) from the rat neurointermediate pituitary in vitro, whereas the oxytocin (OT) release remained unchanged. Naloxone, however, did not significantly alter the spontaneous VP and OT release. Dynorphin (1-17) (10(-7) M) increased the electrically evoked release of VP and OT, while 10(-6) M had a significant, somewhat less pronounced stimulatory effect only on VP, but not on OT release. The opiate inactive fragment [des-Tyr1]dynorphin (1-17) did not change the evoked VP and OT release, indicating that the dynorphin effect was mediated by opiate receptors. beta-Endorphin (10(-6) M and 10(-7) M) did not alter the evoked VP and OT secretion. 10(-6) M [Leu]enkephalin induced a stimulation of the evoked OT, but not VP release; 10(-7) M [Leu]enkephalin had no effect, neither on VP nor on OT release. The opiate antagonist naloxone (10(-5) M) induced an increase in the evoked VP and, even more pronounced, OT release. In a concentration of 10(-6) M, however, naloxone only increased the evoked OT release. When naloxone and dynorphin (1-17) were concomitantly applied, their stimulatory effects on the evoked VP and OT release were additive. Similarly to the effects of naloxone, addition of a monoclonal antibody which binds to the common N-terminal sequence of all endogenous opioid peptides, resulted in a marked increase in the evoked secretion of VP and, to an even more pronounced degree, of OT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of various opioid peptides on vasopressin and oxytocin release from the rat pituitary in vitro. 615 15

Dynorphin-A-(1-8), an opioid peptide widely distributed in the rat central nervous system, is present in vasopressin-containing neurosecretory cells terminating in the neural lobe of the pituitary. Electron microscopic immunocytochemistry reveals that dynorphin-A-(1-8) is contained within the same neurosecretory vesicles as vasopressin and vasopressin-associated neurophysin in the neural lobe of the rat. The results indicate that dynorphin may be released in the pituitary concomitantly with vasopressin during the antidiuretic response.
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PMID:Dynorphin-A-(1-8) is contained within vasopressin neurosecretory vesicles in rat pituitary. 664 26

Earlier studies have shown the formation of a novel neural lobe after hypophysectomy, an experimental manipulation that causes transection of neurohypophyseal nerve fibers and removal of pituitary hormones. The mechanisms that underly this regenerative process are poorly understood. The localization and number of peptide-immunoreactive (-IR) fibers in the median eminence were studied in normal rats and in rats at different times of survival after hypophysectomy using indirect immunofluorescence histochemistry. The number of vasopressin (VP)-IR fibers increased in the external layer of the median eminence in 5 d hypophysectomized rats. Oxytocin (OXY)-IR fibers decreased in the internal layer and progressively extended into the external layer. At long survival times (9 and 16 months) both VP- and OXY-IR fibers had a bilayered distribution occupying both the external and internal layers. Double-labeling experiments combining VP and tyrosine hydroxylase antisera as well as OXY and growth hormone-releasing factor antisera showed that injured neurosecretory fibers growing into the external layer displaced fibers from parvocellular cells originally located there. As a result, there was essentially an inversion in the distribution of these fibers within the median eminence. Galanin (GAL)- and cholecystokinin (CCK)-IR fibers exhibited a similar pattern of distribution after the lesion. Thus, after 5 d there was an increase in GAL- and CCK-IR fibers in the internal layer. At 14 and 30 d, the number of GAL- and CCK-IR fibers progressively decreased, but after longer survivals (9 and 16 months) there was a dramatic reappearance. Dynorphin (DYN)-LI showed a dramatic increase at all levels of the median eminence at short survival times after hypophysectomy, followed by a subsequent decrease to a final stage of a few, strongly immunoreactive fibers in the external layer at longer survival times. Vasoactive intestinal polypeptide (VIP)- and peptide histidine-isoleucine (PHI)-IR fibers in hypophysectomized animals had already contacted portal vessels 5 d after hypophysectomy, and from then on progressively increased in numbers. Finally, most of the peptide fibers described above formed dense innervation patterns around the large blood vessels along the lateral borders of the median eminence. The present results show that hypophysectomy induces a wide variety of changes in hypothalamic neurosecretory fibers. Not only is the expression of several peptides in these fibers modified following different survival times, but a reorganization of the distribution of immunoreactive fibers within the median eminence is demonstrated. The hypothesis is raised that regeneration of injured neurosecretory fibers may be dependent on changes in the expression of peptides possessing trophic actions.
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PMID:Reorganization of neural peptidergic systems in the median eminence after hypophysectomy. 752 31

Dynorphin-A is an endogenously released hormone that is now recognized as a kappa-opioid receptor agonist. Because kappa-agonists have been reported to induce water diuresis through negative modulation of antidiuretic hormone release and/or action, in the present study we investigated the aquaretic effects and safety of E2078, a metabolically stable dynorphin-A analog, in 21 healthy subjects after single (1.0, 2.0, 3.0, 5.0, 7.5 and 10.0 mg, i.m.) and repeated (5.0 mg t.i.d. for 4 and 1/3 days) administration. E2078 dose-dependently increased the 0 to 4-hr urine volume, which plateaued between 1032.4 +/- 130.1 and 1286.2 +/- 113.0 ml/4 hr (mean +/- S.E.M.) at doses of between 5.0 and 10.0 mg. The drug decreased urine osmolality (Uosm) markedly, by 17 to 27%, and the free-water clearance (CH2O) became positive, changing from -1.8 +/- 0.2 (placebo) to 0.8 +/- 0.3-2.8 +/- 0.4 ml/min after a single E2078 administration (P < .01). In the repeated-dose study, the first dose of E2078 increased the 0 to 5-hr urine output (1256 +/- 164.9 ml/5 h), lowered Uosm (151.8 +/- 13.3 mOsm/kg) and brought about a positive CH2O (1.9 +/- 0.2 ml/min). These values were similar to those seen after the single dose, but after the subsequent doses these aquaretic effects were attenuated, although the ranges of these same parameters were still significantly greater (P < .01-0.05) (441.4 +/- 102.4-585.3 +/- 131.9 ml/5 hr, 322.8 +/- 21.9-378.2 +/- 47.7 mOsm/kg and -0.2 +/- 0.2-(-)0.6 +/- 0.2 ml/min, respectively) than the day -1 base line (164.1 +/- 41.3 ml/5 hr, 992.0 +/- 80.6 mOsm/kg and -1.2 +/- 0.2 ml/min, respectively). Urinary excretion of electrolytes (Na, K and Cl) was not altered during either study period. A single E2078 administration reduced plasma antidiuretic hormone dose-dependently. On repeated dosing, the plasma concentration had rebounded to approximately 3 pg/ml by the time of the first dose on days 3 and 5, which lowered it again. The present results suggest that E2078 is a safe and effective aquaretic and could be a useful therapeutic tool for patients with water-retaining diseases.
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PMID:Aquaretic effect of the stable dynorphin-A analog E2078 in the human. 791 98

The effects on vasopressin (VP) release of three dynorphin-A fragments and two antidynorphin antisera were tested in vivo and in vitro. In vivo, the order of potency to inhibit VP release 30 min upon i.c.v. injection was: dynorphin-A-(1-17) > dynorphin-A-(1-13) > dynorphin-A-(1-8). l.c.v. co-administration of 10 nmoles of the specific endopeptidase-inhibitor cFPAAF-pAB and dynorphin-A-(1-8) also suppressed VP secretion. Dynorphin-A-(1-17) antiserum enhanced VP release 20 and 60 min after i.c.v. injection. The antiserum that recognized dynorphin-A-(1-13) elevated VP plasma levels at 60 min post-injection. In vitro, dynorphin-A-(1-8) suppressed electrically evoked VP release from the isolated neural lobe. VP release was not affected by dynorphin-A-(1-13), dynorphin-A-(1-17), naloxone, or by the anti-dynorphin antisera. These data indicate that dynorphin-A-(1-17), rather than dynorphin-A-(1-8), plays a role in the centrally located control of neurohypophysial VP release, whereas dynorphin-A-(1-8) is involved in the control located in the posterior pituitary. The synthetic intermediate fragment dynorphin-A-(1-13) appears to affect VP release both centrally and peripherally.
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PMID:Dynorphin-A and vasopressin release in the rat: a structure-activity study. 793 24

Pial artery constriction following fluid percussion brain injury (FPI) is associated with elevated CSF dynorphin and beta-endorphin concentration in newborn pigs. Additionally, dynorphin is a dilator under control conditions and a vasoconstrictor under decreased cerebrovascular tone conditions. Vasopressin contributes to beta-endorphin-induced pial constriction and the constrictor potential for dynorphin. Recently, it has been observed that FPI reverses vasopressin from a dilator to a constrictor. The present study was designed to characterize the effect of FPI on beta-endorphin-induced constriction and the role of vasopressin in that constriction as well as in the reversal of dynorphin's vascular response following FPI. Brain injury of moderate severity (1.9 - 2.3 atm) was produced in anesthetized newborn pigs equipped with a closed cranial window. Dynorphin in physiologic and pharmacologic concentrations (10(-10), 10(-8), 10(-6) M) was reversed from a dilator to a constrictor following FPI (7 +/- 1, 11 +/- 1, and 16 +/- 1 vs -4 +/- 1, -7 +/- 1, and -11 +/- 1% before and after FPI, respectively). Dynorphin-induced vascular changes were accompanied by increased cortical periarachnoid CSF vasopressin and these biochemical changes were potentiated following FPI (24 +/- 4 vs 134 +/- 7 and 53 +/- 7 vs 222 +/- 14 pg/mliter for control and dynorphin (10(-6) M) before and after FPI, respectively). In contrast, in animals pretreated with the vasopressin receptor antagonist [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid) 2-(O-methyl)-Tyr-AVP] (MEAVP, 5 micrograms/kg iv), dynorphin-induced constriction following FPI was attenuated (6 +/- 1, 12 +/- 1, and 16 +/- 1, vs -2 +/- 1, -4 +/- 1, and -7 +/- 1% before and after FPI, respectively). Additionally, beta-endorphin-induced pial constriction was potentiated following FPI (-7 +/- 1, -10 +/- 1, -15 +/- 1 vs -10 +/- 1 -15 +/- 2, and -21 +/- 2% for beta-endorphin (10(-10), 10(-8), 10(-6) M) before and after FPI, respectively). beta-endorphin-induced CSF vasopressin release was similarly potentiated following FPI. Further, MEAVP blunted the augmented constrictor responses to beta-endorphin observed following FPI (-5 +/- 1, -9 +/- 1, -14 +/- 1 vs -2 +/- 1, -5 +/- 1, and -8 +/- 1% before and after FPI, respectively). These data indicate that FPI potentiates beta-endorphin-induced pial construction and reverses dynorphin from a dilator to a constrictor. Additionally, these data show that vasopressin contributes to augmented beta-endorphin pial constriction and the reversal of dynorphin's vascular effects following FPI. Further, since CSF dynorphin and beta-endorphin concentrations are increased following FPI, these data suggest that these two opioids contribute to pial artery constriction observed following FPI, at least, in part, via the release of vasopressin.
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PMID:Role of vasopressin in altered pial artery responses to dynorphin and beta-endorphin following brain injury. 896 21

Because pial artery dilation during a 20- or 40-min hypoxic exposure was less than that observed during a 5- or 10-min exposure, stimulus duration determines the vascular response to hypoxia. Dynorphin (Dyn) modulates hypoxic pial dilation and contributes to decremented dilation during longer hypoxic exposures. This study was designed to determine whether vasopressin (VP) contributes to Dyn modulation of hypoxic pial dilation in newborn pigs equipped with a closed cranial window. Moderate (M) and severe (S) hypoxia (arterial PO2 approximately 35 and 25 mmHg, respectively) had no effect on cerebrospinal fluid VP during a 5-min exposure but increased its concentration during longer exposure periods. The VP antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Me-Tyr2, Arg8]vasopressin (MEAVP) had no influence on pial dilation during the 5-min exposure but potentiated the 20- and 40-min M and S hypoxic exposure dilations: 21 +/- 2 vs. 29 +/- 3% and 23 +/- 2 vs. 33 +/- 2% for 20- and 40-min S hypoxic dilation before and after MEAVP. Topical VP during 5 min of hypoxia elicited dilation that was reversed to vasoconstriction during 20 min of S and 40 min of M and S hypoxia. Similarly, during 5 min of hypoxia, Dyn elicited dilation that was reversed to vasoconstriction during longer hypoxic periods. MEAVP blunted this Dyn-induced vasoconstriction. These data show that VP modulates hypoxic pial dilation in a stimulus duration-dependent manner and that VP contributes to the reversal of Dyn from a dilator to a constrictor during prolonged hypoxia. Finally, these data suggest that VP contributes to Dyn modulation of hypoxic cerebrovasodilation.
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PMID:Vasopressin contributes to dynorphin modulation of hypoxic cerebrovasodilation. 984 6

Phasic activity in magnocellular neurosecretory cells is characterized by alternating periods of activity (bursts) and silence. During phasic bursts, action potentials are superimposed on plateau potentials that are generated by summation of depolarizing after-potentials. Dynorphin is copackaged in vasopressin neurosecretory vesicles that are exocytosed from magnocellular neurosecretory cell dendrites and terminals, and both peptides have been implicated in the generation of phasic activity. Here we show that somato-dendritic dynorphin release terminates phasic bursts by autocrine inhibition of plateau potentials in magnocellular neurosecretory cells recorded intracellularly from hypothalamic explants using sharp electrodes. Conditioning spike trains caused an activity-dependent reduction of depolarizing after-potential amplitude that was partially reversed by alpha-latrotoxin (which depletes neurosecretory vesicles) and by nor-binaltorphimine (kappa-opioid receptor antagonist), but not by an oxytocin/vasopressin receptor antagonist or a micro-opioid receptor antagonist, indicating that activity-dependent inhibition of depolarizing after-potentials requires exocytosis of an endogenous kappa-opioid peptide. kappa-Opioid inhibition of depolarizing after-potentials was not mediated by actions on evoked after-hyperpolarizations since these were not affected by kappa-opioid receptor agonists or antagonists. Evoked bursts were prolonged by antagonism of kappa-opioid receptors with nor-binaltorphimine and by depletion of neurosecretory vesicles by alpha-latrotoxin, becoming everlasting in approximately 50% of cells. Finally, spontaneously active neurones exposed to nor-binaltorphimine switched from phasic to continuous firing as plateau potentials became non-inactivating. Thus, dynorphin coreleased with vasopressin generates phasic activity through activity-dependent feedback inhibition of plateau potentials in magnocellular neurosecretory cells.
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PMID:Autocrine feedback inhibition of plateau potentials terminates phasic bursts in magnocellular neurosecretory cells of the rat supraoptic nucleus. 1518 Nov 59

Most neurons in the central nervous system co-express peptides alongside their principal transmitter, yet the function of these peptides is largely unknown. Vasopressin neurons of the hypothalamic supraoptic nucleus and paraventricular nucleus contain among the highest concentrations of dynorphin found in the brain. Dynorphin, an endogenous opioid peptide, is co-localized in the same neurosecretory vesicles as vasopressin and is released alongside vasopressin from the dendrites and axon terminals of vasopressin neurons. We and others have shown that neuropeptide release from the soma and dendrites of vasopressin neurons activates vasopressin receptors and kappa-opioid receptors to cause activity-dependent modulation of vasopressin neuron activity, and that this is essential for activity patterning in vasopressin neurons.
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PMID:Somatodendritic dynorphin release: orchestrating activity patterns of vasopressin neurons. 1795 21


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