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)

A monoclonal antibody (mAb L6) to a small-cell lung carcinoma surface antigen recognizes a common epitope of vasopressin-neurophysin and oxytocin-neurophysin in hypothalamic nuclei. We now report on the identification of a neurophysin-like precursor in human lung carcinoma (LX-1) cell membrane. mAb L6 immunoaffinity chromatography of solubilized membranes resulted in a single band of approximately 45 kDa. Western blot analysis demonstrated immunoreactivity of this band with mAb L6, anti-vasopressin, and an antibody to the vasopressin precursor, pro-pressophysin. N-terminal sequencing of this band demonstrated a 21-amino acid homology with the N terminus of human pro-pressophysin, and substitution of a Cys33 residue in the tumor antigen with Arg33. Absence of immunoreactivity with the antibodies described above in cytosolic extracts and culture medium suggests nonsecretion of processed or intact pro-pressophysin-like peptide. Northern analysis of LX-1 mRNA with a 30-mer to the C terminus of rat pro-pressophysin resulted in a band of approximately 1000 base pairs, 250 base pairs larger than hypothalamic message. In situ hybridization of LX-1 tumor-bearing nude rat brain with the same probe demonstrated specific hybridization in rat hypothalamus and xenografted tumor. These findings suggest expression of a pro-pressophysin-like protein in this tumor cell line that is preferentially targeted to the cell membrane.
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PMID:Expression of neurophysin-related precursor in cell membranes of a small-cell lung carcinoma. 170 22

Quiescent Swiss 3T3 cells can be stimulated to reenter the cell cycle by various mitogens used in synergistic combinations with insulin-like growth factors (IGFs). The cells constitutively secrete an IGF-binding protein (IGFBP), which can modulate the interaction of IGFs with their receptors and could, therefore, alter cellular responsiveness to IGFs. We have now characterized the IGFBP secreted by Swiss 3T3 cells and tested whether its secretion is regulated by heterologous mitogens. Ligand blotting using [125I]IGF-I revealed a major IGFBP of 40,000 mol wt, and treatment of the cells with tunicamycin reduced the mol wt of this protein to about 32,000. mRNA from Swiss 3T3 cells hybridized to a 32P-labeled oligonucleotide (50-mer) complementary to rat IGFBP-3. Taken together, these results indicate that the principal IGFBP secreted by Swiss 3T3 cells is probably the N-glycosylated IGFBP-3. Production of this IGFBP by Swiss 3T3 cells was stimulated by 50-150% by the mitogens bombesin, vasopressin, platelet-derived growth factor, epidermal growth factor, and 12-O-tetradecanoylphorbol 13-acetate and also by IGF-I. The increased production of IGFBP was first detected after 4-6h of incubation and was then maintained for 48-72 h. Agents that elevate intracellular cAMP and the glucocorticoid dexamethasone reduced IGFBP output. In cells in which protein kinase-C had been down-modulated, the stimulation of IGFBP output by 12-O-tetradecanoylphorbol 13-acetate was abolished, but the stimulation induced by the other mitogens was not prevented. Thus, the production of IGFBP by Swiss 3T3 cells can be regulated by a number of different signalling pathways.
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PMID:Mitogens regulate the production of insulin-like growth factor-binding protein by Swiss 3T3 cells. 170 79

We studied the interaction properties of synthetic antisense (AS) peptides encoded in the antisense strand of DNA corresponding to the N-terminal 20-residue sequence of the biosynthetic precursor of Arg8-vasopressin (AVP) and its binding protein bovine neurophysin II (BNPII). Binding affinities of sense polypeptides AVP and BNPII with AS peptides were measured by analytical affinity chromatography, in each case by the extent of chromatographic retardation of a soluble polypeptide interactor on an affinity matrix containing the other interactor as the immobilized species. Chromatographically calculated dissociation constants ranged from 10(-3) to 10(-6) M. Experiments were carried out to define the selectivity and underlying forces involved in the AS peptide interactions. For AS peptide elutions on sense peptide affinity supports, reduced binding affinity with increasing 1-propanol concentration and ionic strength suggested the presence of both ionic and hydrophobic contributions to AS peptide/immobilized sense peptide recognition. This same conclusion was reached with the antisense peptides as the immobilized species and measurement of elution of sequence-simplified, truncated, and charge-depleted forms of sense peptides. Immobilized AS 20-mer affinity matrix differentially retarded AVP versus oxytocin (OT) and BNPII versus BNPI (the neurophysin related biosynthetically to OT) and was used to separate these polypeptides from acid extracts of bovine posterior pituitaries. In addition, immobilized AS 12-mer corresponding to AVP-Gly-Lys-Arg could be used to separate AVP from OT. The results confirm that antisense peptides recognize sense peptides with significant selectivity in the AVP/BNPII precursor case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recognition properties of antisense peptides to Arg8-vasopressin/bovine neurophysin II biosynthetic precursor sequences. 260 22

A 25 mer synthetic oligonucleotide, complementary to a specific region of the oxytocin-neurophysin preprohormone messenger RNA (mRNA), was designed for its application to in situ hybridization histochemistry. The probe was 3'-end labeled with [3H] deoxycytidine triphosphate (dCTP) by using terminal deoxynucleotidyl transferase, and hybridization of the labeled probe to the mRNA in the rat hypothalamus was visualized autoradiographically. Hybridization products were specifically localized in the dorsal part of the supraoptic nucleus and the peripheral part of the paraventricular nucleus. Not only is the oligomer designed useful for distinguishing oxytocin from vasopressin gene expressing neurons, but also it is proving useful for studies of estrogen-progesterone effects on neurons in the paraventricular nucleus. Thus, these results indicate that in situ hybridization histochemistry with synthetic oligonucleotide can be a valuable approach to measuring gene expression in hypothalamic neuroendocrine cells.
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PMID:In situ hybridization histochemistry with oxytocin synthetic oligonucleotide: strategy for making the probe and its application. 340 53

Antisense oligodeoxynucleotides (AS-ODN) to AT1 receptor mRNA inhibit high blood pressure in Spontaneously Hypertensive Rats (SHR) when injected into the brain. The effect is presumably through inhibition of the actions of brain angiotensin II (Ang II). Central injection of Ang II elicits several physiological responses including release of vasopressin and motivation to drink. The angiotensin II type-I (AT1) receptor is located in brain regions which have been implicated in mediating these effects. Therefore we hypothesized that AS-ODN to AT1 mRNA would inhibit the drinking and AVP response to central administration of Ang II in adult male SHR. AS-ODN were constructed to bases +63 to +77 (15-mer) of the AT1 receptor RNA. 24 h after AS-ODN treatment (50 micrograms/4 microliters) (intracerebroventricularly, i.c.v.), the drinking response to Ang II (50 ng, i.c.v.) was significantly reduced in the SHR (P < 0.05). The drinking response to Ang II (i.c.v.) was also reduced in the Sprague-Dawley rats (P < 0.05). There was no reduction of water intake in the control animals treated with scrambled ODN (SC-ODN). Repeated injection of AS-ODN did not produce a greater reduction in drinking response. Arginine vasopressin (AVP) release to central Ang II was significantly decreased after AS-ODN treatment when compared to vehicle (P < 0.05) and to SC-ODN injections (P < 0.05). Radioligand binding assays of the hypothalamic block after AS-ODN treatment showed a significant decrease of AT1 receptor binding (P < 0.05). The results show that the antisense inhibition of brain AT1 receptor gene expression decreases the Ang II induced drinking and AVP release responses.
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PMID:Antisense oligonucleotide to AT1 receptor mRNA inhibits central angiotensin induced thirst and vasopressin. 771 85

In this study, in situ hybridization histochemistry was used to determine the regional and cellular localization of vasopressin-neurophysin II (AVP) mRNA in the sheep brain and pituitary with an 35S-labelled synthetic 45-mer oligonucleotide probe complementary to the bovine AVP gene. The highest densities of labelled cell bodies were found in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and suprachiasmatic nucleus (SCN) of the hypothalamus, though such cells were also found in other regions of the diencephalon, including the accessory magnocellular nuclei. Labelled cells were also observed sparsely distributed in every major cortical field as well as in choroid plexus and the pineal gland. No AVP mRNA-expressing cells were found in the bed nucleus of the stria terminalis, the amygdala, or in the medulla and brainstem. In the pituitary, a dense AVP mRNA signal was observed in the intermediate lobe whereas, cells in the anterior or neural lobe did not express AVP mRNA. The dense population of AVP-expressing neurons in both magnocellular and parvocellular fields of the hypothalamus support major roles of AVP in both posterior and anterior pituitary function. Finally, the extrahypothalamic distribution of AVP mRNA transcripts suggest that vasopressinergic neurons may be involved in diverse physiological functions, including the regulation of pineal function and cognition.
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PMID:Distribution and cellular localization of vasopressin mRNA in the ovine brain, pituitary and pineal glands. 841 48

There is evidence that chronic ethanol treatment (CET) disrupts the biological rhythms of various brain functions and behaviors. Because the suprachiasmatic nucleus (SCN) is widely recognized as the dominant pacemaker of the circadian system, we have examined the effects of CET and withdrawal on the main morphological features and chemoarchitecture of this hypothalamic nucleus. Groups of rats ethanol-treated for 6 and 12 months were compared with withdrawn rats (ethanol-treated for 6 months and then switched to a normal diet for an additional 6 months) and with groups of age-matched control and pair-fed control rats. The volume and the total number of neurons of the SCN were estimated from conventionally stained material, whereas the total number of astrocytes and of neurons containing vasopressin (AVP), vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and somatostatin (SS) were estimated from immunostained sections. The estimates were obtained using unbiased stereological methods, based on Cavalieri's principle and the optical fractionator. The volume of the SCN and the total number of SCN neurons and astrocytes did not vary among groups. We found, however, that CET induced a significant reduction in the total number of AVP-, VIP-, GRP-, and SS-containing neurons. Withdrawal from alcohol did not reduce but rather augmented the loss of VIP- and GRP-immunoreactive neurons. The CET-induced neurochemical alterations seem to result from a decrease in neuropeptide synthesis, as revealed by the reduction in AVP and VIP mRNA levels demonstrated by in situ hybridization with radioactively labeled 48-mer AVP and 30-mer VIP probes. It is thus possible to conclude that the irreversible CET-induced changes in the neurochemistry of the SCN might underpin the disturbances in circadian rhythms observed after long-term alcohol consumption.
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PMID:Chronic alcohol consumption and withdrawal do not induce cell death in the suprachiasmatic nucleus, but lead to irreversible depression of peptide immunoreactivity and mRNA levels. 900 74

Rapid effects of antisense oligodeoxynucleotides (AODNs) on the function of the neurohypophysial system have been reported previously. The present studies were designed to determine the effects of vasopressin (VP) and oxytocin (OT) AODNs on osmotically or potassium-stimulated VP and OT release from perifused hypothalamoneurohypophysial (HNS) explants. The AODNs were 18-mer phosphorothioate forms targeted toward the translation initiation sites of either VP or OT mRNA, or a mixed base sequence (4 microM). The explants were exposed to a ramp increase in NaCl (either 20 or 30 mosmol/6 h) or to 25 mM KCl. VP and OT release was measured by radioimmunoassay in sequential 20-min fractions of the perifusate. There was a peptide-specific inhibition by the AODNs of osmotically stimulated VP and OT release. VP AODN inhibited VP, but not OT release, and vice vorsa. However, the AODNs had no effect on potassium-stimulated peptide release, demonstrating that depolarization-secretion coupling was still intact. Furthermore, there were no significant differences in VP and OT mRNA and peptide content after antisense treatment. Thus these observations indicate that acute exposure to peptide AODNs interrupts osmotically stimulated VP and OT release in a peptide-specific manner.
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PMID:Effects of antisense oligodeoxynucleotides on peptide release from hypothalamoneurohypophysial explants. 917 35

Experiments were carried out in stressful foot shock and noise stimulated male Sprague Dawlay rats. 3'-end digoxigenin-labeled 26 mer oligonucliotide probe was used to detect the vasopressin (AVP) mRNA in hypothalamic tissues. Dot blotting technique was used in the assessment of AVP mRNA level. The results showed that the tail systolic arterial pressure of rats increased gradually after stressful stimulations of foot shock in combination with noise. The difference in tail systolic blood pressure between control and stimulated rats was statistically significant after 5-day stimulation. By the ninth day, the systolic blood pressure of the stressed rats reached the highest level and maintained thereafter for several days. No significant difference was observed in the AVP-mRNA level between control and stressed rats by the time when stimulated for 4 days, but it significantly increases when stimulated for 6 days or longer (by the 6th day: P < 0.005; by the 15th day: P < 0.001). No difference was found in plasma osmolalities between control and stressed animals. These results indicate that the stressful foot shocks in combination with noise stimulations may cause an increase in AVP-mRNA level in the hypothalamus, which was accompanied by an increase in systolic arterial pressure. The mechanism of increase in AVP-mRNA level upon stress stimulation remains to be elucidated.
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PMID:[Effect of stressful stimulations on hypothalamic vasopressin mRNA level of rats]. 981 3

A class of diuretic/aquaretic agents based on mirror-image oligonucleotides (so-called Spiegelmers) has been identified. These molecules directly bind and inhibit the neuropeptide vasopressin (AVP). AVP is the major regulatory component of body fluid homeostasis mediated through binding to the renal V(2) receptor. Elevated plasma levels of AVP are implicated in several pathological conditions, mainly cardiovascular diseases. In congestive heart failure, AVP is part of a neuroendocrine imbalance that is responsible for progressive worsening of the disease. Employing in vitro selection techniques, RNA aptamers that bind to the unnatural d-configuration of AVP were isolated. The best aptamer displayed an affinity to d-AVP of approximately 560 pM at 37 degrees C. The corresponding Spiegelmer, a 38-mer mirror-image oligonucleotide (l-RNA) termed NOX-F37, inhibits vasopressin-dependent activation of V(1a) as well as V(2) receptors with IC(50) values of 6.1 nM and 1 nM, respectively. NOX-F37 administered to healthy rats effectively neutralized AVP and increased diuresis dose-dependently for 24 h. The mode of action was strictly aquaretic, i.e., the increase in urine volume was not accompanied by an increase in electrolytes. These results clearly prove the in vivo efficacy of NOX-F37 and points out its potential as a drug in the treatment of diseases that are associated with body fluid overload.
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PMID:An L-RNA-based aquaretic agent that inhibits vasopressin in vivo. 1654 36


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