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)

The primary structure of an elephant neurophysin, homologous to vasopressin-associated neurophysins, is reported. The protein contains a Tyr for Asn substitution at position 75, a position in direct contact with residues 77 and 78 of the monomer-monomer interface. This Tyr residue therefore serves as a potential reporter of the path involved in the long-range linkage between peptide binding and dimerization in this system. NMR studies of the protein in unliganded and liganded states demonstrated normal dimerization properties and the expected increase in dimerization associated with binding peptide. In keeping with an elevated pKa of 11.1 assigned to Tyr-75 by UV spectrophotometric titration, the NMR signals from the 3,5 and 2,6 ring protons of Tyr-75 were shifted 0.3 and 0.2 ppm upfield, respectively, relative to their positions in small peptides, indicating significant shielding and/or hydrogen bonding. The Tyr-75 ring proton signals narrowed slightly, with no discernible change in chemical shift, on conversion from dimer to monomer in the unliganded state. Ring protons of Tyr-49, distant from the monomer-monomer interface, but adjacent to the peptide-binding site, were markedly perturbed by dimerization, in accord with their behavior in bovine neurophysins. The results suggest that the secondary and tertiary structure of the region 75-78 is largely unchanged by dimerization, and argue against an important role for this region in dimerization-mediated conformational changes that alter the binding site in the unliganded state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid sequence and properties of vasopressin-associated elephant neurophysin. 782 4

The aim of the study was to assess whether changes in gastric mucosal blood flow induced by acute normovolaemic anaemia influence the susceptibility of the gastric mucosa to ethanol-induced damage, and the relationship of these changes with nitric oxide biosynthesis. Acute normovolaemic anaemia, promoted by exchanging 3 ml of blood by a plasma expander, induced a significant increase in gastric mucosal blood flow measured by hydrogen gas clearance, without changes in arterial blood pressure. After intragastric 60% ethanol administration, gastric blood flow was still significantly higher in anaemic than in control rats, and this was associated with a lower macroscopic and microscopic gastric damage. Following ethanol administration, anaemic rats pretreated with an inhibitor of nitric oxide biosynthesis (L-NMMA, 50 mg/kg, i.v.) had a lower gastric blood flow and a higher macroscopic gastric damage than anaemic rats without pretreatment. Anaemic rats pretreated with vasopressin also had after ethanol administration a lower gastric blood flow and a higher macroscopic gastric damage. It is concluded that acute normovolaemic anaemia protects the gastric mucosa against damage induced by intragastric ethanol. The inhibition of nitric oxide biosynthesis reverts in part this protective effect, and this seems to be related with the capability of nitric oxide to increase gastric mucosal blood flow, since vasoconstriction by a nitric oxide-independent mechanism causes a similar effect.
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PMID:Acute normovolaemic anaemia prevents ethanol-induced gastric damage in rats through a blood flow related mechanism. 787 Jan 97

The plasma membrane composition of virtually all eukaryotic cells is maintained and continually modified by the recycling of specific protein and lipid components. In the kidney collecting duct, urinary acidification and urinary concentration are physiologically regulated at the cellular level by the shuttling of proton pumps and water channels between intracellular vesicles and the plasma membrane of highly specialized cell types. In the intercalated cell, hydrogen ion secretion into the urine is modulated by the recycling of vesicles carrying a proton pumping ATPase to and from the plasma membrane. In the principal cell, the antidiuretic hormone, vasopressin, induces the insertion of vesicles that contain proteinaceous water channels into the apical cell membrane, thus increasing the permeability to water of the epithelial layer. In both cell types, 'coated' carrier vesicles are involved in this process, but whereas clathrin-coated vesicles are involved in the endocytotic phase of water channel recycling, the transporting vesicles in intercalated cells are coated with the cytoplasmic domains of the proton pumping ATPase. By a combination of morphological and functional techniques using FITC-dextran as an endosomal marker, we have shown that recycling endosomes from intercalated cells are acidifying vesicles but that they do not contain water channels. In contrast, principal cell vesicles that recycle water channels do not acidify their lumens in response to ATP. These non-acidic vesicles lack functionally important subunits of the vacuolar proton ATPase, including the 16 kDa proteolipid that forms the transmembrane proton pore. Because these endosomes are directly derived via clathrin-mediated endocytosis, our results indicate that endocytotic clathrin-coated vesicles are non-acidic compartments in principal cells. In contrast, recycling vesicles in intercalated cells contain large numbers of proton pumps, arranged in hexagonally packed arrays on the vesicle membrane. These pumps are inserted into the apical plasma membrane of A-type (acid-secreting) intercalated cells, and the basolateral plasma membrane of B-type (bicarbonate-secreting) cells in the collecting duct. Both apical and basolateral targeting of H(+)-ATPase-containing vesicles in these cells may be directed by microtubules, because polarized insertion of the pump into both membrane domains is disrupted by microtubule depolymerizing agents. However, the basolateral localization of other transporting proteins in intercalated cells, including the band 3-like anion exchanger and facilitated glucose transporters, is not affected by microtubule disruption.
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PMID:Endosomal pathways for water channel and proton pump recycling in kidney epithelial cells. 814 5

The mammalian kidney metabolizes virtually all of the steroid hormones. Corticosterone receptors have been found in the cortical collecting tubule, and at least four metabolites of the hormone have been identified in rat renal tissue and urine. The biologic activity of these metabolites is not completely known. In this study, we examined the functional effects of three of the metabolites of corticosterone on membrane transport in toad and turtle bladders; we also analyzed the oxidoreductase pathways for corticosterone metabolism. In the toad bladder, maximal water flow (vasopressin- and cyclic AMP-stimulated) was unaffected by corticosterone, 11-dehydro-20-dihydrocorticosterone (metabolite I) and 11-dehydrocorticosterone (metabolite IV); maximal water flow was significantly inhibited by 20-dihydrocorticosterone (metabolite II). Sodium transport in the toad bladder was stimulated by corticosterone, 11-dehydrocorticosterone and 20-dihydrocorticosterone. Analysis of the oxidoreductase pathways in this tissue revealed that most of the corticosterone was oxidized to 11-dehydrocorticosterone, a biologically active compound; 11-dehydrocorticosterone was further metabolized to 11-dehydro-20-dihydrocorticosterone, a biologically inactive compound. Only 6% of the parent compound was converted to 20-dihydrocorticosterone. In the turtle bladder, none of the metabolites tested altered hydrogen ion secretion over the time period studied; no significant biotransformation of corticosterone occurred in this tissue. As the metabolites of corticosterone found in toad bladder are the same as those identified in mammalian tissues, our studies suggest that some of them may be important modulators of sodium and water transport in the distal nephron. Our data further suggest that these compounds are likely not involved in the regulation of urinary acidification.
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PMID:Corticosterone metabolism and membrane transport. 816 15

Vasopressin is a potent vasoconstrictor to most blood vessels but is a vasodilator to some. The role of vasopressin in the regulation of nerve blood flow (NBF) is not known. We undertook a dose-effect study of vasopressin on NBF and evaluated its interactions with alpha-adrenoreceptors and its effect on ischemic conduction failure. NBF was measured using microelectrode hydrogen polarography. Vasopressin was administered topically (to epineurium). Topical epineurial application of vasopressin caused a concentration -dependent reductin of NBF (EC 50 = 6.6 x 10(-9) M; asymptote = 73.9% NBF reduction). The topical application of subthreshold concentrations of vasopressin and norepinephrine alone resulted in no change in NBF, but combined application resulted in a dramatic reduction in NBF (72.3%). The ratio of amplitudes of muscle compound action potential evoked on proximal to distal stimulation was used as an index of the presence of an ischemic conduction block. This ratio was significantly reduced following the combined topical application of supramaximal concentrations of vasopressin and norepinephrine. These findings suggest that vasopressin is a potent neural vasoconstrictor and that vasoconstriction caused by combined vasopressin and norepinephrine can produce partial conduction block of sciatic-tibial nerve [corrected].
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PMID:Extreme vasoreactivity of rat epineurial arterioles to vasopressin. 889 22

We compared changes in gastric mucosal blood flow (GMBF) and left gastric artery blood flow (LGABF) in response to pharmacological, physiological, and pathological stimuli. GMBF and LGABF were measured by the hydrogen gas clearance and perivascular ultrasonic transit time techniques, respectively, under baseline conditions and following intravenous infusion of vasopressin or pentagastrin, isovolemic hemodilution, or gastric perfusion with HCl-taurocholate. Blood flow changes following vasopressin or hemodilution were significantly larger in the left gastric artery than in the gastric mucosa. In contrast, the increment in blood flow associated with pentagastrin-stimulated acid secretion was significantly greater in the gastric mucosa than in the extramural artery. Barrier disruption with acid-taurocholate induced similar changes in both measurement sites. The gastric hyperemia induced by either mechanism was significantly attenuated by blockade of NO synthesis. These data demonstrate that although functional changes in GMBF are primarily supported by changes in blood flow at the extramural gastric arteries, the gastric mucosal microvasculature is also under the influence of independent local control mechanisms.
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PMID:Gastric mucosal blood flow regulation in response to different stimuli. 933 Nov 50

By the use of hydrogen gas clearance technique, we have investigated the role of GMBF in the adaptive cytoprotection induced by intragastric perfusion with low concentration prior to high concentration of HCl plus ethanol. The results were as follows: (1) intragastric perfusion with low concentration prior to high concentration of HCl plus ethanol led to an adaptive cytoprotection, i.e., the gross and the deep damage were decreased by 47.09% and 44.57% respectively, as compared with those caused by high concentration of HCl plus ethanol alone; correspondingly, GMBF also showed an adaptive hyperemic response, i.e., GMBF was increased by 28.02% as compared with that due to high concentration alone; (2) close arterial infusion of vasopressin blocked the adaptive hyperemic response and abolished the adaptive cytoprotection; (3) intravenous indomethacin reduced the basal GMBF, and abolished both the adaptive hyperemic response and cytoprotection; furthermore, the gross and deep damage were aggravated compared with that caused by high concentration alone. The results showed that the adaptive hyperemic response of gastric mucosa was involved in the adaptive cytoprotection and suggested that the adaptive cytoprotection of endogenous prostaglandin might be partially related to the increase of GMBF.
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PMID:[Effects of gastric mucosal blood flow (GMBF) on the role of adaptive cytoprotection of rat gastric mucosa]. 938 79

Vasoinhibitory effects of (-)-(S)-2-[3,5-bis(1, 1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3, 4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thiazolidin- 4-one hydrogen fumarate (CP-060S), a synthesized cardioprotective agent, were examined. In the rat aortic rings, the contractile responses to cumulative application of angiotensin II, [Arg(8)]-vasopressin (vasopressin), or prostaglandin F(2alpha) were inhibited by CP-060S in a concentration-dependent manner. The Ca(2+)-induced contractions in the presence of vasopressin or prostaglandin F(2alpha) were also inhibited by CP-060S in a concentration-dependent manner. The inhibitory effect of 10(-5) M CP-060S on phenylephrine-induced contraction was as potent as that of 10(-6) M nifedipine, and the combined addition of 10(-6) M nifedipine and 10(-5) M CP-060S showed the effect similar to that of 10(-5) M CP-060S alone. In rat aorta loaded with a Ca(2+) indicator, fura-PE3, 10(-5) M CP-060S completely inhibited the high K(+)-induced increase in cytosolic Ca(2+) level ([Ca(2+)](i)) and contraction. In contrast, 10(-5) M CP-060S only partially inhibited the increase in [Ca(2+)](i) and contraction due to phenylephrine or prostaglandin F(2alpha). In the presence of 10(-6) M nifedipine, 10(-5) M CP-060S did not inhibit the increase in [Ca(2+)](i) and contraction induced by prostaglandin F(2alpha). In a Ca(2+)-free medium, the phasic increases in contraction and [Ca(2+)](i) induced by phenylephrine were not affected by 10(-5) M CP-060S. These results suggest that the vasoinhibitory effect of CP-060S in rat aortic rings is due mainly to the inhibition of L-type voltage-dependent Ca(2+)-channels.
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PMID:Mechanisms of vasoinhibitory effect of cardioprotective agent, CP-060S, in rat aorta. 1098 38

Quantitative structure-activity relationships (QSARs) of different cardiotonic agents are presented. A critical analysis of all QSARs provides a very vivid picture of the mechanisms of varying cardiotonic agents. The cardiotonics can be broadly put into 2 categories: cardiac glycosides and nonglycoside cardiotonics, which include phosphodiesterase of type III (PDE III) inhibitors, sympathomimetic (adrenergic) stimulants, A1-selective adenosine antagonists, Ca2+ channel activators and vasopressin antagonists. For cardiac glycosides, QSARs reveal that the position of carbonyl oxygen in their lactone moiety and shifting of the lactone ring from its original position or its replacement by another group would be crucial for their activity. The carbonyl group or its isostere like CN is indicated to be the sole binding entity and the hydrogen bonding through this group is considered to be the most likely binding force. For nonglycoside cardiotonics that include PDE III inhibitors and A1-selective antagonists, a five-point model has been established for their activity, the salient features of which are: (1) the presence of a strong dipole, (2) an adjacent acidic proton, (3) a methyl-sized lipophilic space, (4) a relatively flat overall topography and (5) a basic or hydrogen-bond acceptor site opposite to the dipole. For Ca2+ channel activators, the importance of steric, electrostatic, lipophilic and hydrogen-bonding properties of molecules is indicated, while for vasopressin antagonists the lipophilic and electronic properties are suggested to be the most important.
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PMID:Quantitative structure-activity relationships of cardiotonic agents. 1112 65

Oxytocin is a neurohypophyseal peptide hormone that induces labor and lactation in mammals. An inverse gamma-turn mimetic corresponding to the tripeptide Ile-Val-Asn has been synthesized and incorporated instead of residues 3-5 of oxytocin to probe the hypothesis that a gamma-turn involving these residues is found in the receptor bound conformation of oxytocin. In the turn mimetic, residues i and i + 1 are connected by a psi[CH(2)O] isostere while a covalent methylene bridge replaces the hydrogen bond that is often found between residues i and i + 2 in gamma-turns. The turn mimetic was assembled from three types of building blocks: an azido epoxide, an alpha-bromo acid, and a protected beta-amino alcohol. The oxytocin analogue did not induce contractions of the uterus nor did it inhibit oxytocin-induced contractions. It is suggested that the loss of bioactivity is mainly due to the presence of a psi[CH(2)O] isostere instead of an amide bond between residues i and i + 1 in the turn mimetic.
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PMID:Synthesis and pharmacological evaluation of an analogue of the peptide hormone oxytocin that contains a mimetic of an inverse gamma-turn. 1203 59


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