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)

Aprotinin, a reversible inhibitor, and D-Phe-Phe-Arg-chloromethyl ketone (DPPA), an irreversible inhibitor of mammalian glandular kallikreins, decreased short-circuit current (SCC) in the isolated toad urinary bladder. Both were more potent and rapidly acting on the mucosal than serosal surface. The maximal inhibition in basal SCC was 29% for aprotinin and 41% for DPPA at concentrations of 7.0 X 10(-6) and 1.0 X 10(-5) M, respectively. SCC inhibition with mucosal aprotinin was reversed by rinsing, whereas inhibition with mucosal DPPA was not reversible. The presence of either agent in the mucosal bath inhibited the SCC increase to serosal vasopressin, but neither modified this response when present in the serosal bath. Neither agent affected basal or vasopressin-stimulated osmotic water permeability. Aprotinin did not prevent aldosterone-induced increases in SCC. Soybean trypsin inhibitor, an inhibitor of plasma but not glandular kallikrein, did not affect SCC. We postulate that these inhibitors of mammalian glandular kallikreins act upon some accessible serine proteinase(s) to reduce short-circuit current. This protein(s) might be an amphibian homologue of mammalian renal kallikrein.
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PMID:Inhibition of short-circuit current in toad urinary bladder by inhibitors of glandular kallikrein. 615 95

The hypothalamo-neurohypophysial system, containing the hormones oxytocin (OT) and vasopressin (VP) and their associated carrier proteins, the neurophysins (NPS), has been the subject of extensive investigation for more than 40 years. This system has been reinvestigated during the last decade by application of immunocytochemical methods employing the rabbit antisera to the hormones and NPS. In this study we describe the preparation and characterization of a monoclonal antibody to VP and its application in immunohistochemistry. The antibody did not cross-react with OT or arginine vasotocin (AVT). Its antigenic determinants as characterized by absorption with various VP analogs included two aromatic amino acids: Phe in position 3, and to a lesser extent Tyr in 2. Tissue fixation with formaldehyde resulted in inadequate immunostaining as compared to glutaraldehyde, most likely due to interference with the aromatic amino acid determinants by the former fixative.
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PMID:A monoclonal antibody to vasopressin: preparation, characterization, and application in immunocytochemistry. 618 60

The photoreactive analogs of vasopressin, [Phe2,Phe-(p-N3)3]AVP (3a) and [Phe-(p-N3)2]AVP (2a), and the chemically reactive analogs of vasopressin, [Phe2,Phe-(p-NHCOCH2Br)3]AVP (3b) and [Phe-(p-NHCOCH2Br)2]AVP (2c), have been tested in the toad bladder for irreversible stimulation or inhibition of the water permeability response. Analog 3a was found to be an agonist with an ED50 of 4.5 X 10(-7) M and to induce a maximal osmotic water flow across bladders equivalent to 74% of that observed with the parent hormone (AVP). Photolysis of this analog in Ringer's fluid resulted in a decrease in its biological activity, with a half-time of 7 min. However, UV irradiation of the analog in the presence of toad bladders triggered an irreversible increase in the permeability of the bladders to water. Under optimal conditions of irradiation, water permeability remained at about 60% of maximum for more than 3 h after washout of analog 3a. The addition of AVP raised the permeability of these bladders to 100%. Analog 3a did not cause irreversible stimulation without photolysis, nor did this analog induce its characteristic effect when added to the mucosal solution. Compound 2a was found to be a potent antagonist of AVP. This inhibitory action of 2a was readily reversed in both the presence and absence of UV irradiation. Compound 3b was also found to be a reversible inhibitor of AVP. Compound 2c was found to be inactive as agonist or antagonist. These studies suggest that analog 3a binds covalently at or near the toad bladder hydroosmotic receptors, resulting in a persistent increase in permeability to water of the bladder wall.
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PMID:Irreversible stimulation of hydroosmotic response in toad bladder by photoaffinity labeling with [Phe2,Phe-(p-N3)3]Vasopressin. 631 20

The photoreactive analog of vasopressin [1,6-alpha-aminosuberic acid, 3-(p-azidophenylalanine), 8-arginine] vasopressin [( Asu1,6, Phe (p-N3)3]AVP) has been synthesized. This analog retains a high binding affinity for the vasopressin receptor in plasma membranes from bovine kidney inner medulla (apparent dissociation constant, KD = 8.5 X 10(-9) M). [Asu1,6, Phe (p-N3)3] AVP was found to be biologically active in triggering the characteristic increase in toad bladder permeability to water. Photolysis of the analog in the presence of the toad bladder results in a hydroosmotic response which persists, in spite of repeated washings, for more than 18 h. The irreversible stimulation of the bladder is inhibited when photolysis is carried out in the presence of vasopressin. Our findings indicate that with photoactivation [Asu1,6, Phe(p-N3)3]AVP binds covalently to hormonal receptors and forms an active hormone-receptor complex. This analog, therefore, is a suitable tool for studies of hydroosmotic receptor function and for receptor isolation.
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PMID:[1,6-alpha-aminosuberic acid, 3-(p-azidophenylalanine), 8-arginine] vasopressin: a new photoaffinity label for hydroosmotic hormone receptors. Characterization of the ligand and irreversible stimulation of hydroosmotic water flow in toad bladder by photoaffinity labeling. 631 75

The adrenergic amines noradrenaline and adrenaline increased flux through phenylalanine hydroxylase by approx. 50%. This effect, which appears to be mediated by an alpha-adrenergic mechanism, was accompanied by a rapid increase in the phosphorylation of phenylalanine hydroxylase. Although ionophore A23187 mimicked the effects of the adrenergic amines, vasopressin was completely without effect on either phenylalanine hydroxylation or enzyme phosphorylation. Flux through phenylalanine hydroxylase in young rats (80 g) was insensitive to alpha-adrenergic, but sensitive to beta-adrenergic, agents. Consistent with previous observations [Fisher & Pogson (1984) Biochem. J. 219, 79-85] the present data indicate a close correlation between phosphorylation state and flux rate (i.e. enzyme activity).
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PMID:Effects of adrenergic agents, vasopressin and ionophore A23187, on the phosphorylation of, and flux through, phenylalanine hydroxylase in rat liver cells. 642 73

Despite the absence of vasopressin, Brattleboro homozygous (DI) rats concentrate their urine to hypertonic levels when deprived of drinking water for 24 h. Glomerular filtration rate (GFR) falls concurrently and might contribute to the increased concentrating ability. The present studies concerned the time course of the changes in concentrating ability and GFR during the early hours of dehydration. Experiments were performed in 10 chronically catheterized conscious DI rats in the normally hydrated control state and during 3 h of fluid deprivation. Urine osmolality (Uosmol) increased from 97 +/- 6 (SE) to 325 +/- 11 mosmol/kg H2O at 3 h. Averaged over the 3 h, neither GFR nor effective renal blood flow changed significantly (103 +/- 2 and 106 +/- 4% of control, respectively). Fractional excretion of sodium (FENa) rose markedly from 0.3 +/- 0.1 to 1.3 +/- 0.1% at its peak. Clearly, a fall in GFR cannot explain the rise in Uosmol during the first 3 h. Plasma oxytocin (OT) increased from 5.6 +/- 0.8 to 36.4 +/- 4.5 pg/ml after 3 h of dehydration. In additional experiments, d(CH2)5-D-Phe-VAVP, an antidiuretic antagonist (anti-ADH), was administered to eight DI rats after 3-h dehydration. Control, 3-h dehydration, and post-anti-ADH values were, respectively: for Uosmol, 102 +/- 7, 347 +/- 14, 145 +/- 11 mosmol/kg H2O; for GFR, 1,003 +/- 43, 1,042 +/- 59, 866 +/- 54 microliter X min-1 X 100 g body wt-1; for FENa, 0.4 +/- 0.1, 1.4 +/- 0.1, 0.5 +/- 0.1%. The decreases following anti-ADH were all statistically significant. We conclude that OT is released during the early hours of dehydration in the DI rat and has at least three renal effects. It causes a natriuresis, it maintains renal hemodynamics and GFR during the volume contraction, and it elicits a weak antidiuretic response.
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PMID:Antidiuretic effect of endogenous oxytocin in dehydrated Brattleboro homozygous rats. 647 23

As part of a program in which we are attempting (a) to delineate the structural features at positions 1-9 in our previously reported antidiuretic antagonists required for antidiuretic antagonism and (b) to obtain analogues with enhanced antiantidiuretic potency and/or selectivity, we have synthesized 14 new analogues of the antidiuretic antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-D-phenylalanine,4-valine]arginine-vasopressin [d-(CH2)5-D-Phe2VAVP), in which the valine residue at position 4 was replaced by the following L-amino acids and glycine: Ile, Abu, Thr, Ala, Gln, Lys, Cha, Nle, Nva, Phe, Leu, Gly, Tyr, and Pro. These analogues are 1, d-(CH2)5-D-Phe2,Ile4AVP; 2, d(CH2)5-D-Phe2,Abu4AVP; 3, d(CH2)5-D-Phe2,Thr4AVP; 4, d(CH2)5-D-Phe2,Ala4AVP;5, d(CH2)5-D-Phe2AVP; 6, d(CH2)5-D-Phe2,Lys4AVP; 7, d(CH2)5-D-Phe2,Cha4AVP; 8, d(CH2)5-D-Phe2,Nle4AVP; 9, d(CH2)5-D-Phe2,Nva4AVP; 10, d(CH2)5-D-Phe2,Phe4AVP; 11, d(CH2)5-D-Phe2,Leu4AVP; 12, d(CH2)5-D-Phe2,Gly4AVP; 13, d(CH2)5-D-Phe2,Tyr4AVP; 14, d(CH2)5-D-Phe2,Pro4AVP. The protected intermediates required for the synthesis of all of these peptides were prepared by the solid-phase method and cleaved from the resin by ammonolysis. Following deblocking with Na in NH3 and oxidizing with K3[Fe(CN)6], each peptide was purified on Sephadex G-15 in a two-step procedure using 50% HOAc and 0.2 M HOAc as eluants. Analogues 1-14 were tested for agonistic and antagonistic activities by antidiuretic, vasopressor, and oxytocic assays in rats. Analogues 1, 2, and 4-6 exhibit no detectable antidiuretic agonistic activity. All analogues, with the exception of the Pro4-containing analogue, are antidiuretic antagonists. Their antiantidiuretic pA2 values are as follows: 1, 8.24 +/- 0.08; 2, 7.96 +/- 0.07; 3, 7.62 +/- 0.09; 4, 7.52 +/- 0.03; 5, 7.21 +/- 0.07; 6, 7.22 +/- 0.12; 7, 7.19 +/- 0.08; 8, 7.12 +/- 0.09; 9, 6.99 +/- 0.06; 10, 6.07 +/- 0.11; 11, 6.07 +/- 0.11; 12, 5.85 +/- 0.05; 13, approximately 5.57; 14, a weak agonist (0.004 U/mg). Analogues 1-14 also antagonize the vascular responses to arginine-vasopressin (AVP) and the in vitro oxytocic responses to oxytocin. Analogues 1, 2, 3, and 5 have also been shown to antagonize the in vivo oxytocic responses to oxytocin. Five of these analogues (1, 2, 3, 6, and 7) exhibit enhanced antiantidiuretic/antivasopressor selectivity. d(CH2)5-D-Phe2,Lys4AVP and other position-4 analogues with side-chain functional groups may be useful covalent ligands with which to probe the structural characteristics of AVP renal and vascular receptors. With an antiantidiuretic "effective dose" of 0.46 +/- 0.07 nmol/kg and a pA2 value of 8.24 +/- 0.08, d(CH2)5-D-Phe2,Ile4AVP (1) appears to be the most potent antidiuretic antagonist reported to date.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Potent antagonists of the antidiuretic responses to arginine-vasopressin based on modifications of [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-D- phenylalanine,4-valine]arginine-vasopressin at position 4. 663 16

Mesotocin ([Ile8]-oxytocin), lysipressin ([ Lys8]-vasopressin) and phenypressin ([Phe8]-vasopressin) have been identified in the western gray kangaroo (Macropus fuliginosus) as well as four other macropodids. Lysipressin and phenypressin, which differ by the amino acids in positions 2 (Tyr/Phe) and 8 (Lys/Arg) are likely products of two separate vasopressin-like genes. It is assumed that arginine vasopressin found in most mammals is the product of two identical genes which can be revealed in some species by differential mutations as seen usually in marsupials. The duality can also be revealed by differential mutations in another domain of the precursors, such as the neurophysin (MSEL-neurophysin), as observed in the ox.
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PMID:A multigene family for the vasopressin-like hormones? Identification of mesotocin, lysipressin and phenypressin in Australian macropods. 663 61

As part of a program in which we are attempting (a) to obtain more potent and/or more selective antagonists of the antidiuretic responses to arginine-vasopressin (AVP) and (b) to delineate the structural features at positions 1-9 required for antidiuretic antagonism, we have synthesized 13 new analogues of the antidiuretic antagonist [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-D-isoleucine,4- valine]arginine-vasopressin [d(CH2)5[D-Ile2]VAVP] in which the valine residue at position 4 has been replaced by the L-amino acids Abu, Ile, Thr, Ala, Ser, Nva, Gln, Leu, Lys, Cha, Asn, Orn, and Phe and two new analogues of the antidiuretic antagonist [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-D-phenylalanine,4- valine]arginine-vasopressin [d(CH2)5[D-Phe2]VAVP] with the Val4 residue replaced by Ser and Orn. These analogues are 1, d(CH2)5[D-Ile2,Abu4]AVP; 2, d(CH2)5[D-Ile2,Ile4]AVP; 3, d(CH2)5[D-Ile2,Thr4]AVP; 4, d(CH2)5[D-Ile2,Ala4]AVP; 5, d(CH2)5[D-Ile2,Ser4]AVP; 6, d(CH2)5[D-Ile2,Nva4]AVP; 7, d(CH2)5[D-Ile2]AVP; 8, d(CH2)5[D-Ile2,Leu4]AVP; 9, d(CH2)5[D-Ile2,Lys4]AVP; 10, d(CH2)5[D-Ile2,Cha4]AVP; 11, d(CH2)5[D-Ile2,Asn4]AVP; 12, d(CH2)5[D-Ile2,Orn4]AVP; 13, d(CH2)5[D-Ile2,Phe4]AVP; 14, d(CH2)5[D-Phe2,Ser4]AVP; and 15, d(CH2)5[D-Phe2,Orn4]AVP. The protected peptide precursors for these peptides were prepared by the solid-phase method, followed by ammonolytic cleavage. The free peptides 1-15 were obtained by deblocking with Na in NH3, oxidation of the resultant disulfhydryl compounds with dilute K3[Fe(CN)6], and purification on Sephadex G-15 in a two-step procedure with 50% HOAc and 0.2 M HOAc as eluants. Analogues 1-15 were tested in rats for agonistic and antagonistic activities by antidiuretic, vasopressor, and oxytocic assays.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potent and selective antagonists of the antidiuretic responses to arginine-vasopressin based on modifications of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-D-isoleucine,4- valine]arginine-vasopressin at position 4. 670 45

Analogs of [arginine8]vasopressin (AVP) in which the peptide chain was elongated from the N-terminus by the addition of Ala-Arg-Arg-, Ala-Ala-Phe-, Pro-Arg-Val-, Pro-Ala-Arg-Arg, and Pro-Ala-Ala-Phe-, and from the C-terminus by the addition of -Ala-Met-Ala-NH2 and -Gly-Arg-Arg-Ala-NH2 were synthesized by the solid phase method and purified by Sephadex G-15 chromatography. At the final step of the synthesis, the extent of formation of the intramolecular disulfide bond was found to be sequence dependent. These peptides were incubated with extracts of the rat hypothalamus (supraoptic region) and neural lobe and with isolated neurosecretory granules from the neural lobe, and the release of vasopressin was measured by the rat pressor assay. All peptides resisted conversion to the hormone in the presence of tissue extracts, except (Ala-Ala-Phe)-AVP which was converted to AVP in the presence of all three tissue extracts at pH 4.7 but not at pH 8.0. When these peptides were treated with trypsin, chymotrypsin, or leucine aminopeptidase at pH 8.0, only the action of chymotrypsin on [Ala-Ala-Phe]AVP resulted in AVP formation. Evidence obtained using lysosomal enzyme markers suggested that the converting enzyme activity in neurosecretory granule preparations was not of lysosomal origin.
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PMID:Extended chain analogs of [arginine8]vasopressin as model prohormones: investigation of precursor-processing enzymes in extracts of the rat hypothalamus and neural lobe. 675 99


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