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

Administration of the 1-deamino-arginine8 vasopressin caused a decrease in right, but not left, atrial levels of atriopeptin (AP) in chloral hydrate-anesthetized rats. The amount of exogenous AP required to match the 1-deamino-arginine8 vasopressin-stimulated plasma levels of AP was equivalent to the decrease in AP content of the right atrium, suggesting that resynthesis of AP did not occur within the 60 min after 1-deamino-arginine8 vasopressin stimulation. The correlation between increased plasma levels and decreased atrial content was also observed in bilaterally nephrectomized rats, suggesting that the kidney is not a major site of degradation of AP in vivo. This finding was confirmed by the comparison of the half-life of exogenous AP in normal (T1/2 = 31 sec) and nephrectomized (T1/2 = 64 sec) animals. Plasma immunoreactivity of the N-terminal fragment of the prohormone (which is also released after cleavage of the precursor peptide) increased 35-fold by 24 hr after nephrectomy in comparison with a 5-fold increase in AP. Half-life studies of the N-terminal fragment suggest that the kidney is the major site of degradation of this molecule. This study demonstrated the different kinetics and renal metabolism of the AP and N-terminal portions of the prohormone.
 ...
PMID:Atriopeptin turnover: quantitative relationship between in vivo changes in plasma levels and atrial content. 294 22

The postnatal development of several pro-enkephalin-B-derived opioid peptides - dynorphin 1-17, dynorphin 1-8, dynorphin B, alpha-neo-endorphin and beta-neo-endorphin - was examined in rat pituitary lobes. The concentrations of pro-enkephalin-B-derived peptides from the anterior pituitary were between 4- and 12-fold and those from the neurointermediate pituitary between 17- and 122-fold lower in newborn as compared to adult rats. Similarly, the concentrations of vasopressin in the neurointermediate pituitary increased 50-fold between birth and adulthood; those of oxytocin, however, increased more than 540-fold over this period. The molecular weight pattern of dynorphin 1-17, dynorphin 1-8, dynorphin B, alpha- and beta-neo-endorphin-immunoreactive peptides in the anterior and neurointermediate pituitary did not differ between 3-day-old pups and adult rats. In the neurointermediate pituitary, the major immunoreactive components had the same chromatographic properties as synthetic dynorphin 1-17, dynorphin 1-8, dynorphin B, alpha- and beta-neo-endorphin, respectively, on gel filtration and high-performance liquid chromatography (HPLC). This indicates that neonatal rats were already capable of processing the precursor pro-enkephalin B into these various opioid peptides. In newborn rats, however, the amount of dynorphin 1-8 in the neurointermediate pituitary was three times lower than that of its putative intermediate precursor peptide dynorphin 1-17. Similarly, the amount of beta-neo-endorphin was almost four times lower than that of its putative precursor alpha-neo-endorphin. In contrast, in the neurointermediate pituitary of adult rats, dynorphin 1-17 and dynorphin 1-8, in addition to a alpha- and beta-neo-endorphin, occurred in equimolar amounts.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ontogenetic development of the pro-enkephalin B (= pro-dynorphin) opioid peptide system in the rat pituitary. 615 Nov 28

[he concentrations of immunoreactive (ir-) peptides derived from the opioid peptide precursors proenkephalin A (Met-enkephalin), proenkephalin B [dynorphin (DYN)-(1-17), dynorphin-(1-8), dynorphin B, alpha-neoendorphin (alpha-NEO-E), beta-NEO-E] and proopiomelanocortin [beta-endorphin (beta-END)], and of the neurosecretory hormones vasopressin and oxytocin increased between approximately 10-fold and 50-fold from birth to adulthood in the rate hypothalamus. Gel filtration and HPLC analysis of proenkephalin B-derived opioid peptides revealed that in 3-day-old rats the predominant portion of ir-dynorphin-(1-17) and a substantial part of ir-dynorphin B consisted of a high (6000) mol wt species, a common precursor peptide for DYN-(1-17) and DYN B. In adults rats, however, authentic DYN-(1-17) and DYN B were found to be the major ir-forms. The mol wt patterns of ir-DYN-(1-8), ir-alpha-NEO-E and ir-beta-NEO-E did not differ between 3-day-old and adult rats and reflected predominantly the respective authentic opioid peptides. Taking into consideration the developmental changes in the mol wt pattern of ir-DYN-(1-17), authentic DYN-(1-17) was 5 times lower in concentration than DYN-(1-8) in 3-day-old rats, whereas in adults these opioid peptides occurred in equimolar concentrations. These findings suggest that the posttranslational processing of the precursor proenkephalin B changes in the course of postnatal development. Ir-beta-END in the hypothalamus of newborn and adult rats consisted exclusively of beta-END-sized peptides which were not (unlike those in the intermediate pituitary lobe) alpha-N-acetylated. Thus, in the hypothalamus, the enzymatic processing of the opioid peptide precursor proopiomelanocortin to beta-END seems to be fully active at birth, in contrast to that of proenkephalin B.
 ...
PMID:Evidence for a differential postnatal development of proenkephalin B (= prodynorphin)-derived opioid peptides in the rat hypothalamus. 654 67

In order to clarify the role of neurokinin B (NKB), the dynamic changes in NKB expression and synthesis following water deprivation were examined in the arginine-vasopressin (AVP) neurons of hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. In intact rats, NKB and AVP showed almost the same high level of immunohistochemical reactivity in the magnocellular neurons of the PVN and SON, as well as in the varicose fibers in the median eminence (ME). In contrast, NKB precursor peptide (NKBp) immunoreactivity in the SON and PVN were relatively weak. Five days after water deprivation, AVP and NKB immunoreactivity decreased drastically, while NKBp-immunoreactivity increased in both the PVN and SON magnocellular neurons. Reverse transcription-polymerase chain reaction analysis of control animals revealed high levels of AVP mRNA and substantial amounts of NKB mRNA in the SON. This was contrast to the relatively low levels of AVP mRNA and undetectable levels of NKB mRNA in the PVN. After five days of water deprivation, AVP mRNA in the PVN and NKB mRNA in both the PVN and the SON increased considerably. These results indicate that synthesis and release of NKB, which colocalizes to AVP neurons, are enhanced by water deprivation in the same manner as AVP in the PVN and SON. Thus, NKB seems to be involved in the central control of body fluid levels. The results also suggest that the production rate of NKB under normal conditions in SON dominant.
 ...
PMID:Effects of water deprivation on neurokinin B production by the arginine-vasopressin neurons of hypothalamic paraventricular and supraoptic nuclei. 1141 Oct 93

The fluoresceinyl (Flu) group has been linked by an amide bond to the side chain amino group at position 8 of (a) two oxytocin (OT) antagonists, to give d(CH(2))(5)[Tyr(Me)(2),Thr(4),Orn(8)(5/6C-Flu),Tyr-NH(2)(9)]VT (Orn(8)(5/6C-Flu)OTA) (1) and desGly-NH(2),d(CH(2))(5)[D- Tyr(2),Thr(4),Orn(8)(5/6C-Flu)]VT (2), and (b) eight Lys(8) and Orn(8) analogues of potent OT agonists, to give d[Lys(8)(5/6C-Flu)]VT (3), d[Thr(4),Lys(8)(5/6C-Flu)]VT (4), [HO(1)][Lys(8)(5/6C-Flu)]VT (5), [HO(1)][Thr(4),Lys(8)(5/6C-Flu)]VT (6), d[Orn(8)(5/6C-Flu)]VT (7), d[Thr(4),Orn(8)(5/6C-Flu)]VT (8), [HO(1)][Orn(8)(5/6C-Flu)]VT (9), and [HO(1)][Thr(4),Orn(8)(5/6C-Flu)]VT (10). The tetramethylrhodamyl (Rhm) group was attached to the precursor peptide of 9 to give [HO(1)][Orn(8)(5/6C-Rhm)]VT (11). All 11 fluorescent peptides were evaluated in human OT and vasopressin V(1a) (vasoconstrictor), V(1b) (pituitary), and V(2) (antidiuretic) receptor binding and functional assays. With K(d) = 6.24, 217, >10000, and >10000 nM for the OT, V(1a), V(1b), and V(2) receptors, peptide 1 is a potent and selective fluorescent OT antagonist and may be useful for specifically labeling OT receptors while peptide 2 exhibits low affinities for all the receptors. The fluorescent peptides 3-10 are all very potent agonists for the human OT receptor. They exhibit the following K(d) values (nM) for the human OT, V(1a), V(1b), and V(2) receptors, respectively: (3) 0.29, 57, 124, >10000; (4) 1.8, 25.5, 150, >10000; (5) 0.34, 13.7, 66, nd (not determined); (6) 0.32, 17.3, 53, >10000; (7) 0.25, 107, 393, >10000; (8) 0.40, 30, 282, >10000; (9) 0.18, 12.2, 126, nd; (10) 0.17, 11.8, 87, >1000; (11) 0.092, 7.36, nd, nd. Peptide 7 exhibits both a high affinity and a high selectivity for human OT receptors. Peptides 7 and 11 were utilized to study the internalization of the OT receptor-ligand complex. Preliminary studies indicate that this process is similar to that observed for the vasopressin V(1a) receptor and differs from that observed for vasopressin V(2) receptors. Some or all of the fluorescent OT antagonists and agonists reported here are very promising new fluorescent ligands for labeling cells which express the human OT receptor and are also useful tools to follow endocytosis of the receptor-ligand complex.
 ...
PMID:Synthesis and characterization of fluorescent antagonists and agonists for human oxytocin and vasopressin V(1)(a) receptors. 1203 67

Vasopressin is one of the key regulators of the body's water and solute balance. When this balance is pathologically disturbed, determination of serum vasopressin concentrations might be a helpful tool for guiding therapy. However, due to its instability and considerable association to platelets, reliable measurement of circulating vasopressin is difficult to achieve, if at all. In search of a more robust way for quantifying vasopressin release, we identified copeptin, a glycopeptide with unknown function, as an alternative diagnostic target. Since copeptin is derived from the same precursor peptide as vasopressin, released amounts of copeptin should mirror those of vasopressin. With a newly developed sensitive sandwich immunoassay, we detected strongly elevated concentrations of fully processed copeptin in serum of septic shock patients. The magnitude of elevation and the high stability of copeptin in serum and plasma indicate that copeptin measurement is not affected by the problems, which are associated with the direct measurement of vasopressin, and thus is apparently suitable to indirectly determine the release of vasopressin.
 ...
PMID:Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. 1592 90

Arginine vasopressin (AVP or antidiuretic hormone) is one of the key hormones in the human body responsible for a variety of cardiovascular and renal functions. It has so far escaped introduction into the routine clinical laboratory due to technical difficulties and preanalytical errors. Copeptin, the C-terminal part of the AVP precursor peptide, was found to be a stable and sensitive surrogate marker for AVP release. Copeptin behaves in a similar manner to mature AVP in the circulation, with respect to osmotic stimuli and hypotension. During the past years, copeptin measurement has been shown to be of interest in a variety of clinical indications, including cardiovascular diseases such as heart failure, myocardial infarction, and stroke. This review summarizes the recent progress on the diagnostic use of copeptin in cardiovascular and renal diseases and discusses the potential use of copeptin measurement in the context of therapeutic interventions with vasopressin receptor antagonists.
 ...
PMID:Copeptin: a biomarker of cardiovascular and renal function. 2065 10

Stress is defined as anything that throws the body out of homeostatic balance; for example an acute illness. Any stressor which activates the hypothalamo-pituitary-adrenal (HPA) axis leads to an increase in concentrations of the adrenal stress hormone, cortisol. One of the major hypothalamic stress hormones, which is stimulated by different stressors, is vasopressin (AVP). However, measurement of circulating AVP levels is challenging because it is released in a pulsatile pattern, it is unstable and is rapidly cleared from plasma. AVP derives from a larger precursor peptide (pre-provasopressin) along with copeptin which is released in an equimolar ratio to AVP and is more stable in the circulation and easy to determine. Copeptin levels were found to closely mirror the production of AVP. We have shown that copeptin more subtly mirrors the individual stress level compared to cortisol. Due to the positive association of copeptin with the severity of illness and outcome, copeptin has been proposed as a prognostic marker in acute illness. The prognostic accuracy of copeptin has been analysed in sepsis, pneumonia, lower respiratory tract infections, stroke and other acute illnesses. Thereby, copeptin was found to accurately mirror disease severity and to discriminate patients with unfavourable outcomes from patients with favourable outcomes. Copeptin improves the prognostic information provided by commonly used clinical scoring instruments. Importantly, interpretation of copeptin levels must always consider the clinical setting. An accurate prognostic assessment has the potential to guide interventions and effectively plan and monitor rehabilitation and, thus optimise the management of individual patients and the allocation of limited health care resources. Future intervention studies must prove the value of copeptin in clinical decision making and in improving the overall medical management of patients with acute illnesses.
 ...
PMID:The stress hormone copeptin: a new prognostic biomarker in acute illness. 2087 95

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department.
 ...
PMID:The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department. 2226 20

Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, holds promise as a diagnostic and prognostic plasma biomarker in various acute clinical conditions. Factors influencing copeptin response in the critical care setting are only partially established and have not been investigated systematically. Using an in vivo infant ventilation model (Wistar rats, 14 days old), we studied the influence of commonly occurring stressors in critically ill children. In unstressed ventilated rats basal median copeptin concentration was 22pmol/L. In response to respiratory alkalosis copeptin increased 5-fold, while exposure to hypoxemia, high PEEP, hemorrhage, and psycho-emotional stress produced a more than 10-fold increase. Additionally, we did not find a direct association between copeptin and acidosis, hypercapnia, and hyperthermia. Clinicians working in the acute critical care setting should be aware of factors influencing copeptin plasma concentrations. Moreover, our results do have implications for animal studies in the field of stress research.
 ...
PMID:Determinants of plasma copeptin: a systematic investigation in a pediatric mechanical ventilation model. 2312 68


1