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)

An acute reserpine treatment has the same selective and marked depleting effect on corticoliberin-like immunoreactivity as on vasopressin-like immunoreactivity in the rat zona externa of the median eminence. Somatostatin and gonadoliberin immunoreactivities appear unmodified. Reserpine effect is blocked by pretreatment with monoamine oxidase inhibitors (pargyline or tranylcypromine). Present results support the notion of an inhibitory role of monoamines, particularly catecholamines, on the release of corticoliberin.
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PMID:Reserpine-induced depletion of corticoliberin (CRF)-like immunoreactivity in the zona externa of the rat median eminence. 660 76

The indirect immunofluorescence technique was used to examine the pharmacology associated with reserpine-induced alterations in vasopressin and neurophysin (VP/NP) immunoreactivity in the external layer of the median eminence in the rat. Twenty-four hours after injection of reserpine, a selective, marked depletion of VP/NP immunoreactivity from the external layer is apparent. Pretreatment with the monoamine oxidase inhibitors, pargyline and tranylcypromine, prevents the depleting effect of reserpine, indicating that the acute effect of reserpine is mediated by monoamines. Acute intraventricular treatment with 6-hydroxydopamine, but not 5,7-dihydroxytryptamine, mimicked the reserpine effect, suggesting that catecholamines mediate reserpine depletion of VP/NP immunoreactivity from the external layer. The experimental results are consistent with a regulatory model in which catecholamines tonically inhibit VP/NP release from terminals in the external layer of the median eminence. Although the studies do not definitively determine the functional relationship between VP and ACTH, the anatomical location of these terminals, the dramatic change in the VP/NP content of these terminals in response to reserpine, and the lack of a response to dehydration suggest that this pool of vasopressin may contribute to ACTH hypersecretion in response to reserpine.
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PMID:Terminals of reserpine-sensitive vasopressin-neurophysin neurons in the external layer of the rat median eminence. 701 84

1. Neurotransmitters released from nerve endings are inactivated by re-uptake into the presynaptic nerve terminals and possibly into neighbouring glial cells. While analysing the functional properties of alpha 1-adrenoceptors in the hypothalamus, we observed a high-affinity uptake process for noradrenaline in postsynaptic peptidergic neurones. 2. In primary hypothalamic cell cultures and in a hypothalamic neuronal cell line, [3H]-prazosin bound with high affinity and was displaced by unlabelled prazosin in concentrations of 10(-10) to 10(-7) M. However, at concentrations of unlabelled prazosin above 10(-7) M, there was a paradoxical increase in apparent [3H]-prazosin binding. 3. Methoxamine, an alpha 1-adrenoceptor ligand that is not subject to significant neuronal uptake, displaced [3H]-prazosin but did not cause the paradoxical increase in the apparent binding of [3H]-prazosin. Cooling the cells to 4 degrees C reduced the total amount of prazosin associated with the cells; under these conditions, methoxamine almost completely inhibited [3H]-prazosin binding to the cells. 4. In the presence of desipramine (DMI), unlabelled prazosin displaced [3H]-prazosin as before, but no paradoxical increase in apparent binding was seen above 10(-7) M. 5. The paradoxical increase of [3H]-prazosin binding was not observed in membrane preparations of hypothalamic neurones. These findings indicated that the paradoxical increase in apparent [3H]-prazosin binding was due to a cellular uptake process that becomes evident at high concentrations of the ligand. 6. DMI (10(-5) M) had no effect on the specific binding of [3H]-prazosin. The presence of alpha1-adrenoceptors was confirmed by binding of [125]-HEAT, but [3H]-idazoxan (an alpha2- ligand) did not bind to the cells.7. The uptake of prazosin obeyed the Michaelis-Menten model, with similar Km and Vmax values in both types of cultures.8. Noradrenaline was taken up with high affinity by both types of cultures. (+/-)-[3H]-noradrenaline uptake was reduced by DMI and by excluding sodium from the medium, indicating that this process has some of the properties of uptake 1. (+/-)-[3H]-noradrenaline uptake in the cell line was unaffected by testosterone.9. The measured uptake of (-)-noradrenaline in the cell line was considerably increased by blockade of catechol-omicron-methyl-transferase and monoamine oxidase, suggesting that (-)-noradrenaline is metabolized to lipophilic products that escape across the plasma membrane.10. Studies in rats, in which the noradrenaline isomer 6-hydroxydopamine was used, suggested that the post synaptic uptake process is operative in hypothalamic CRH and vasopressin neurones in vivo.11. The Km for (-)-noradrenaline was within the range for the high affinity uptake, process in noradrenergic neurones. Uptake takes place in concentrations at which noradrenaline activates alpha1-adrenoceptors.Removal of noradrenaline from the vicinity of the receptors may prevent desensitization,thus maintaining the responsiveness of postsynaptic neurones to the actions of the neurotransmitter.
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PMID:High-affinity uptake of noradrenaline in postsynaptic neurones. 835 34

Phenylephrine, a potent stimulator of cardiomyocyte glucose transport (GT), caused a rapid rise in cytosolic Ca2+ by 30%. Agents inducing a similar Ca2+ response did not stimulate (angiotension II, vasopressin) or inhibited GT by 20% (elevated extracellular Ca2+). Stimulation of GT by phorbol myristate acetate was additive to both phases of phenylephrine's effect (4 min, 60 min). Phenylephrine had no influence on the adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels. Agents raising cAMP (isoproterenol) or cGMP (e.g., nitroprusside) did not stimulate GT. Wortmannin (inhibitor of 1-phosphatidylinositol 3-kinase) suppressed the action of insulin on GT but not that of phenylephrine. In contrast, the Na+/H+ exchange inhibitor amiloride (which blocks phenylephrine-induced cytosolic alkalinization or even lowers cellular pH) depressed the effect of phenylephrine by 50%, whereas insulin-stimulated GT was little affected. However, raising extracellular pH up to 8.4 failed to increase GT. Lowering pH to 6.8 decreased phenylephrine's effect by 40% whereas insulin-dependent GT was not significantly altered. Clorgyline, tranylcypromine (monoamine oxidase inhibitors), and added catalase suppressed the slow phase of phenylephrine's action, whereas amiloride also affected the fast phase. We conclude that 1) stimulation of cardiomyocyte GT by phenylephrine does not involve cAMP, cGMP, or 1-phosphatidylinositol 3-kinase; 2) protein kinase C activation cannot explain the full extent of stimulation; 3) Ca2+ release or cytosolic alkalinization may be required but is not sufficient to trigger phenylephrine's action, and 4) the slow phase of stimulation is mediated by the monoamine oxidase-dependent degradation of phenylephrine and by the resulting H2O2 formation.
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PMID:Signals mediating stimulation of cardiomyocyte glucose transport by the alpha-adrenergic agonist phenylephrine. 892 48

Animal experiments have already shown that neurotransmitters and neuropeptides are not only important for normal functioning of the adult central nervous system (CNS) but are also crucial to its development. However, information on the spatio-temporal distribution of these endogenous substances in the developing human CNS is still scarce. With the use of immunocytochemical staining and a constant supply of properly fixed human abortuses from southern China, an early appearance of acetylcholinesterase, enkephalin, and substance P immunoreactivities was detected first in the spinal cord (weeks 5 to 7 of gestation), then in the brainstem nuclei (weeks 11 to 12). Their overlapping localizations in many regions of the CNS suggest possible interactions among neurons containing these substances, which are in turn important for the proper establishment of the neuronal circuitry. Immunoreactivity for neuropeptide Y appeared initially in the lateral region of upper segments of the spinal cord at week 12 of gestation, then spread latero-medially and cranio-caudally to the sacral region. In the hippocampus, neuropeptide Y neurons appeared from week 15 onwards. Serotoninergic neurons were found in the dorsal raphe nucleus at week 10 and then decreased in number as the fetus grew older. Somatostatin releasing inhibitory factor, vasopressin, and oxytocin were detected in the hypothalamus from weeks 12 to 14 onwards, and monoamine oxidase, succinic dehydrogenase, parvalbumin, calbindin D28K, and vasoactive intestinal peptide were found in the visual cortex at midgestation. The early appearance and the abundance of the neurotransmitters and neuropeptides in the developing CNS indicate that they may play a key role in neuronal differentiation.
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PMID:Early appearance of acetylcholinergic, serotoninergic, and peptidergic neurons and fibers in the developing human central nervous system. 1040 66

Noradrenaline and serotonin are known to control arginine-vasopressin (AVP) and oxytocin (OT) secretion in the systemic circulation. The aim of the current study was to investigate whether these monoamines are also able to influence AVP and OT expression in the paraventricular (PVN) and supraoptic nuclei (SON). To test this hypothesis, we used the Tg8 transgenic mice KO for the monoamine oxidase-A gene, which present high levels of noradrenaline and serotonin in the brain. AVP and OT expression were evaluated at peptide and mRNA levels by immunohistochemistry, enzyme immunoassay, and in situ hybridization. Compared with wild type, the amounts of AVP, OT, AVP mRNA, and OT mRNA were increased in the PVN and SON in Tg8 mice. To distinguish the respective contributions of noradrenaline and serotonin to these modifications, we treated Tg8 mice with a synthesis inhibitor of either catecholamines [alpha-methylparatyrosine (alpha-MPT)] or serotonin [parachlorophenylalanine (pCPA)]. Administration of alpha-MPT to Tg8 mice induced a decline in the amounts of AVP, OT, and their mRNA in the PVN and SON. The pCPA treatment in Tg8 mice was also associated with a decrease in OT expression in the PVN and SON and in AVP expression in the PVN, but not in the SON. These results suggest that noradrenaline may activate AVP and OT expression in the PVN and SON. Likewise, serotonin is proposed to stimulate AVP and OT expression in the PVN and only OT expression in the SON.
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PMID:Activation by serotonin and noradrenaline of vasopressin and oxytocin expression in the mouse paraventricular and supraoptic nuclei. 1188 Apr 81

The effect of chronic exposure to carbofuran (4.5 ppm in static water) for six months on the gonadal histophysiology and hypothalamo-neurohypophyseal complex was studied in Channa punctatus. Experimental observations revealed significant inhibition of gonadal development with associated degenerative abnormalities as evidenced by ovarian and testicular histology and reduced gonadosomatic index. Degenerative changes in ovary were exihibited by stage I (oogonium) and stage II (immature/non-vitellogenic) oocytes as marked by perinuclear ooplasmic lysis, clumping and dissolution resulting in disintigration of nuclear material altogether attributed to complete degeneration of such oocytes. Testicular deleterious changes included degeneration of spermatogenic elements and necrosis of interstitial cells of Leydig. Correlative histophysiological changes were also observed in the pituitary gonadotrophs and hypothalamic, nucleus pre-opticus, neurons that were smaller, inactive and less in number with associated necrosis. Corresponding to the changes in nucleus pre-opticus neurons, significant inhibition of brain monoamine oxidase enzyme activity was also recorded in treated group. These observations suggest that carbofuran even at low concentration level under long-term exposure is capable of inducing retardation of gonadal development which might have been mediated through the impairment of the hypothalamo-neurohypophyseal-gonadal axis in this species.
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PMID:Carbofuran induced impairment in the hypothalamo-neurohypophyseal-gonadal complex in the teleost, Channa punctalus (Bloch). 1201 60

Since the introduction of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) in mid-1950's, treatment of depression has been dominated by monoamine hypotheses. The well-established clinical efficacy of TCAs and MAOIs is due, at least in part, to the enhancement of noradrenergic or serotonergic mechanisms, or to both. Unfortunately, their very broad mechanisms of action also include many unwanted effects related to their potent activity on cholinergic, adrenergic and histaminergic receptors. The introduction of selective serotonin reuptake inhibitors (SSRIs) over twenty years ago had been the next major step in the evolution of antidepressants to develop drugs as effective as the TCAs but of higher safety and tolerability profile. During the past two decades SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram) gained incredible popularity and have become the most widely prescribed medication in the psychiatric practice. The evolution of antidepressants continued resulting in introduction of selective and reversible monoamine oxidase inhibitors (eg. moclobemid), selective noradrenaline (eg. reboxetine), dual noradrenaline and serotonin reuptake inhibitors (milnacipram, venlafaxin, duloxetin) and drugs with distinct neurochemical profiles such as mirtazapine, nefazadone and tianeptine. Different novel serotonin receptor ligands have also been intensively investigated. In spite of the remarkable structural diversity, most currently introduced antidepressants are 'monoamine based'. Furthermore, these newer agents are neither more efficacious nor rapid acting than their predecessors and approximately 30% of the population do not respond to current therapies. By the turn of the new millennium, we are all witnessing a result of innovative developmental strategies based on the better understanding of pathophysiology of depressive disorder. Several truly novel concepts have emerged suggesting that the modulation of neuropeptide (substance P, corticotrophin-releasing factor, neuropeptide Y, vasopressin V1b, melanin-concentrating hormone-1), N-methyl-D-aspartate, nicotinic acetylcholine, dopaminergic, glucocorticoid, delta-opioid, cannabinoid and cytokine receptors, gamma-amino butyric acid (GABA) and intracellular messenger systems, transcription, neuroprotective and neurogenic factors, may provide an entirely new set of potential therapeutic targets, giving hope that further major advances might be anticipated in the treatment of depressive disorder soon. The goal of this review is to give a brief overview of the major advances from monoamine-based treatment strategies, and particularly focus on the new emerging approaches in the treatment of depression.
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PMID:Trends in the development of new antidepressants. Is there a light at the end of the tunnel? 1507 74

Atypical depression has been linked to low hypothalamic-pituitary-adrenocortical axis activity and exhibits physical and affective symptoms resembling those of glucocorticoid deficiency. Because atypical depression has also been defined by preferential responsiveness to monoamine oxidase inhibitors (MAO-I), we hypothesized that MAO-I reverse these abnormalities by interfering with glucocorticoid feedback and increasing hypothalamic-pituitary-adrenocortical activity. To test this hypothesis, we measured plasma hormones and ACTH secretagogue gene expression in male C57BL/6 mice treated chronically with saline vehicle or phenelzine, a representative MAO-I. Changes in glucocorticoid feedback were evaluated using adrenalectomized (ADX) mice with and without corticosterone replacement. Antidepressant efficacy was confirmed by decreased immobility during forced swim testing. Phenelzine significantly increased circadian nadir and postrestraint plasma corticosterone levels in sham-operated mice, an effect that correlated with increased adrenocortical sensitivity to ACTH. Phenelzine increased circadian nadir, but not poststress ACTH in ADX mice, suggesting that phenelzine augmented corticosterone secretion in sham-operated mice by increasing stimulation and decreasing feedback inhibition of hypothalamic-pituitary activity. Consistent with the latter possibility, phenelzine significantly increased plasma ACTH and paraventricular hypothalamus CRH mRNA in ADX, corticosterone-replaced mice. Phenelzine did not increase paraventricular hypothalamus CRH or vasopressin mRNA in ADX mice lacking corticosterone replacement. We conclude that chronic phenelzine treatment induces sustained increases in glucocorticoids by impairing glucocorticoid feedback, increasing adrenocortical responsiveness to ACTH, and increasing glucocorticoid-independent stimulation of hypothalamic-pituitary activity. The resulting drive for adrenocortical activity could account for the ability of MAO-I to reverse endocrine and psychiatric symptoms of glucocorticoid deficiency in atypical depression.
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PMID:Chronic treatment with the monoamine oxidase inhibitor phenelzine increases hypothalamic-pituitary-adrenocortical activity in male C57BL/6 mice: relevance to atypical depression. 1556 36

Spontaneously hypertensive rats (SHR) pathologically elevate blood pressure with age. This elevation is accompanied by specific neuronal degeneration in the hypothalamus and enlargement of the lateral ventricles. The aim of this study was to assess the neuroprotective effect of the monoamine oxidase B (MAO-B) inhibitor, rasagiline on paraventricular (PVN) hypothalamic degeneration in SHR. The S-enantiomer of rasagiline, S-PAI, a much weaker MAO inhibitor, and two antihypertensive drugs, captopril and hydralazine were also tested. Normotensive Wistar Kyoto (WKY) rats served as controls. One month-old SHR or WKY rats were treated daily for 3-4 months. Systolic blood pressure was recorded, parvocellular vasopressin (VP) immunopositive cells were counted and the area of the third ventricle measured. In saline-treated SHR, blood pressure rose significantly and the number of VP parvocellular cells was reduced by about 60% relative to WKY. Rasagiline, 1 mg/kg/day, reduced PVN neuronal cell death in SHR up to 112% relative to saline-treated SHR; 0.3 mg/kg/day exerted a smaller but significant effect. These actions were accompanied by parallel reductions in systolic blood pressure. Captoril, hydralazine and S-PAI did not prevent death of VP neurons. In SHR, the volume of the third ventricle was about double that of WKY. Rasagiline significantly prevented this ventricular dilation. These results indicate than rasagiline protects from cell death in an in vivo animal model in a dose-dependant manner and could be of use as a neuroprotector in the central nervous system.
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PMID:Neuroprotective effect of rasagiline, a monoamine oxidase-B inhibitor, on spontaneous cell degeneration in a rat model. 1576 64


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