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)

It is proposed that the scope of solid-phase peptide synthesis could be considerably broadened by attaching peptides to the solid-phase through functional side-chain groups rather than through the commonly used alpha-carboxyl groups. Side-chain attachment offers the use of a large variety of chemical linkages to solid supports. Attachment through the epsilon-amino group of the lysine residue to a polystyrene resin has been applied to a solid-phase synthesis of lysine-vasopressin. N(alpha)-tert-butyl-oxycarbonyl-L-lysyl-glycinamide was condensed with chloroformoxymethyl polystyrene-2% divinylbenzene resin. After removal of the N(alpha)-protecting tert-butyloxycarbonyl group, the peptide chain was elongated by standard Merrifield procedures to give Tos-Cys(Bzl)-Tyr-Phe-Glu-(NH(2)) - Asp(NH(2)) - Cys(Bzl) - Pro - Lys(Z - resin) - Gly-NH(2). Cleavage from the resin with HBr in dioxane or trifluoroacetic acid gave a partially protected nonapeptide hydrobromide. For purification, it was converted into a fully protected peptide by treatment with benzyl p-nitro-phenyl carbonate and crystallized. Deprotection by sodium in liquid ammonia, oxidative cyclization, IRC-50 desalting, and ion-exchange chromatography gave lysinevasopressin with high potency in a rat-pressor assay.
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PMID:Solid-phase synthesis with attachment of peptide to resin through an amino acid side chain: (8-lysine)-vasopressin. 528 May 19

The effect of peritubular and luminal pH changes on hydraulic conductance, (Lp, 10(-7) cm X s-1 X atm-1) in the isolated perfused rabbit cortical collecting tubule (CCT) was tested at 37 degrees C before and after administration of 20 microU/ml vasopressin or 10(-4) M 8-[p-chlorophenylthio]-adenosine cyclic monophosphate (8-CPT-cAMP). In vasopressin experiments when bath pH was changed from 7.58 to 7.16 or from 7.58 to 6.70, mean Lp decreased from 249 +/- 32 to 199 +/- 23 (n = 5; P less than 0.01) and from 231 +/- 38 to 201 +/- 36 (n = 5; NS), respectively. In contrast, in 8-CPT-cAMP experiments when bath [HCO3] was kept constant while CO2 was elevated the hydroosmotic response was increased. Using 2.5 mM HCO3, Lp at 0.4% CO2 was 275 +/- 15 and at 6% CO2 it was 352 +/- 50 (n = 4; paired t test; P less than 0.05). At 8.5 and 21.5 mM HCO3 raising CO2 from 2 to 13% and from 4 to 32% increased Lp from 237 +/- 71 to 410 +/- 32 (n = 4; paired t test; P less than 0.05) and from 282 +/- 45 to 449 +/- 63 (n = 6; paired t test; P less than 0.001), respectively. Reducing luminal pH from 7.40 to 5.40 had no effect on either vasopressin- or cAMP-induced changes in Lp. Accordingly, lowering the bath pH by increasing the PCO2 at constant [HCO3] markedly stimulates the response to 8-CPT-cAMP, whereas lowering the bath pH by reducing [HCO3] inhibits the vasopressin response.
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PMID:pH effect on osmotic response of collecting tubules to vasopressin and 8-CPT-cAMP. 630 11

To study the mechanisms by which antidiuretic hormone and prostaglandins regulate Na transport at the apical membranes of the cells of anuran tissues, studies were done with fluctuation analysis. Epithelia of frog skin (Rana pipiens) were treated with vasopressin alone, or treated with vasopressin after inhibition of Na transport by indomethacin. The tissues were bathed symmetrically with a Cl-HCO3 Ringer solution and short-circuited continuously. In this experimental circumstance, the amiloride-induced current noise power density spectra were of the Lorentzian type with little or no l/f noise, provided that "scraped" skins were used for study. Despite large changes of Na transport, especially in epithelia treated with indomethacin and vasopressin, the single-channel Na current remained essentially unchanged, whereas the density of amiloride-inhibitable, electrically conductive Na channels was increased by vasopressin and decreased by indomethacin.
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PMID:Hormonal control of apical membrane Na transport in epithelia. Studies with fluctuation analysis. 631 38

Because lithium salts are widely used for long-term therapy of affective disorders and have been recently implicated as a cause of tubulointerstitial renal disease, we have undertaken experiments designed to establish the site of the early and late pathologic lesions and to determine their correlation with the lithium-induced concentrating defect. Male Wistar rats given a semisynthetic diet that contained lithium carbonate, 90 mEq/kg dry weight, developed serum lithium levels in the human therapeutic range; pair-fed controls received sodium carbonate. Within 3 weeks, treated rats developed marked polyuria, with elevation of free water clearance and vasopressin-resistant diabetes insipidus. Early morphologic changes were confined to the cortical collecting tubules and, possibly, contiguous portions of distal tubules. The tubules were dilated and irregularly lined with cells that had bulging or thinned basophilic cytoplasm, enlarged nuclei, sometimes basal vacuolization, and a few mitoses. These changes were evident at 3 weeks and progressed through the end of the observation period at 18 weeks. The proliferative component of the lesion was demonstrated by the finding of a significant and specific increase in 3H-thymidine uptake by nuclei of collecting/distal tubules of lithium-treated rats. The lesion, but not the increased thymidine uptake, extended into the medullary collecting ducts at 9 and 18 weeks. Although occasional intratubular mononuclear cells were seen at 9 and 18 weeks, no interstitial inflammation or fibrosis was seen. These tubular epithelial lesions were not seen in the kidneys of Brattleboro rats or glucose-treated Wistar rats despite comparable polyuria. We suggest that this early, persistent, and reproducible lesion, characterized by reactive and proliferating tubular cells in the cortical collecting tubules, predisposes the kidney to injury from otherwise mild or insignificant insults and may explain the sporadic occurrence of serious tubulointerstitial disease in patients on long-term lithium therapy.
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PMID:Effects of long-term lithium administration on renal structure and function in rats. A distinctive tubular lesion. 671 69

In the rat medullary thick ascending limb (MTAL), hyperosmolality inhibits transepithelial HCO3- absorption (JHCO3-) by inhibiting apical membrane Na+/H+ exchange. To examine signaling mechanisms involved in this regulatory response, MTALs were isolated and perfused in vitro with 25 mM HCO3- solutions (290 mosmol/kg H2O). Osmolality was increased in lumen and bath solutions by addition of 300 mM mannitol or 75 mM NaCl. Addition of mannitol reduced JHCO3- by 60% and addition of NaCl reduced JHCO3- by 50%. With the protein tyrosine kinase (PTK) inhibitor genistein (7 microM) or herbimycin A (1 microM) in the bath, addition of mannitol reduced JHCO3- only by 11% and addition of NaCl reduced JHCO3- only by 15%. Staurosporine (10(-7) M) or forskolin (10(-6) M) in the bath had no effect on inhibition of JHCO3- by hypertonic NaCl. Genistein had no effect on inhibition of JHCO3- by vasopressin (a cyclic AMP-dependent process) or stimulation of JHCO3- by prostaglandin E2 (a protein kinase C-dependent process). Under isosmotic conditions, addition of genistein or herbimycin A to the bath increased JHCO3- by 30% through stimulation of apical membrane Na+/H+ exchange. Addition of the tyrosine phosphatase inhibitor molybdate (50 microM) to the bath reproduced the inhibition of JHCO3- observed with hyperosmolality. These data indicate that 1) the effect of hyperosmolality to inhibit MTAL HCO3- absorption through inhibition of apical membrane Na+/H+ exchange is mediated via a PTK-dependent pathway that functions independent of regulation by cyclic AMP and protein kinase C, and 2) a constitutive PTK activity inhibits apical membrane Na+/H+ exchange and HCO3- absorption under isosmotic conditions. Our results suggest that tyrosine phosphorylation is a critical step in inhibition of the apical Na+/H+ exchanger isoform NHE-3 by hyperosmolality.
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PMID:Hyperosmolality inhibits bicarbonate absorption in rat medullary thick ascending limb via a protein-tyrosine kinase-dependent pathway. 773 Mar 71

Animal studies have shown increased fluid absorption from the peritoneal cavity following intraperitoneal (ip) vasopressin. Lithium is known to antagonize vasopressin effects on fluid absorption in kidney distal nephrons. The aim of the present study was to see whether lithium-containing exchanges increase the ultrafiltration rates (UF) during peritoneal dialysis (PD) in rats. PD was carried out in 6 Sprague-Dawley rats with 1.5% dextrose-containing PD solution using 15-ml volumes. Each exchange (ex) took 1 min for inflow, 4 mins for outflow and 25 mins for dwell. All rats underwent 9 consecutive half-hourly exs. During exs 4-6 lithium carbonate 2.5 mM was added to the PD solution. During lithium-containing exs significant increases in the glucose absorption rates (3.9 +/- 7.8 vs 37.5 +/- 8.1 mg/ex; p = 0.025) were associated with significant reductions in the UF (3.03 +/- 0.25 vs 1.78 +/- 0.12 ml/ex; p = 0.005). In conclusion, the isolated increase in glucose absorption without increases in the dialysate protein concentration with ip lithium, may suggest either a selective increase in size of the pores with a mean dimater near that of the glucose molecule or enhanced lymphatic absorption. ip lithium did not increase the UF in a rat model of PD.
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PMID:Lithium carbonate decreases ultrafiltration rates in an experimental model of PD. 774 15

Secretion of bicarbonate has been described for distal nephron epithelium and attributed to apical Cl-/HCO3- exchange in beta-intercalated cells. We investigated the presence of this mechanism in cortical distal tubules by perfusing these segments with acid (pH 6) 10 mM phosphate Ringer. The kinetics of luminal alkalinization was studied in stationary microperfusion experiments by double-barreled pH (ion-exchange resin)/1 M KCl reference microelectrodes. Luminal alkalinization may be due to influx (into the lumen) of HCO3- or OH-, or efflux of H+. The magnitude of the Cl-/HCO3- exchange component was measured by perfusing the lumen with solutions with or without chloride, which was substituted by gluconate. This component was not different from zero in control and alkalotic (chronic plus acute) Wistar rats. Homozygous Brattleboro rats (BRB), genetically devoid of antidiuretic hormone, were used since this hormone has been shown to stimulate H+ secretion, which could mask bicarbonate secretion. In these rats, no evidence for Cl-/HCO3- exchange was found in control BRB and in early distal segments of alkalotic animals, but in late distal tubule a significant component of 0.14 +/- 0.033 nmol/cm2.sec was observed, which, however, is small when compared to the reabsorptive flow found in control Wistar rats, of 0.95 +/- 0.10 nmol/cm2.sec. In addition, 5 x 10(-4) M SITS had no effect on distal bicarbonate reabsorption in controls as well as on secretion in alkalotic Wistar and Brattleboro rats, which is compatible with the absence of effect of this drug on the apical Cl-/HCO3- exchange in other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secretion of HCO3-/OH- in cortical distal tubule of the rat. 776 8

The aim of this article is to consider how a large quantity of potassium (K+) can be excreted without the development of hyperkalemia. The hypothesis will focus on interactions between K+ and HCO3- primarily within the kidneys. It is speculated that the absorption of K+ from the gastrointestinal tract is accompanied by an initial addition of HCO3- to the body; this in turn could, via intrarenal events, promote the delivery of HCO3- to the cortical collecting duct (CCD), where interactions may permit the development of a very high rate of excretion of K+. To test one portion of this hypothesis, studies were performed in sheep because they normally consume approximately 10-fold more K+ per kilogram body weight than do humans. In the absence of a significant degree of anabolism, there is only a limited potential to shift K+ acutely into cells. Hence, an extremely large capacity to excrete K+ is required to avoid a severe degree of hyperkalemia. The excretion of K+ depends primarily on the ability to have a sustained rise in the (K) in each liter of luminal fluid exiting the CCD to very high levels and to have a large number of liters of fluid exit the terminal CCD while antidiuretic hormone is acting. A reasonable approximation of this CCD flow rate can be obtained by examining the osmole excretion rate when ADH acts. Because these sheep excreted 1,650 mosmol (2 L x 827 mosm/kg H2O) per day, a minimum estimate for volume delivery out of the CCD is 5 to 6 L/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potassium excretion: a story that is easy to digest. 787 41

Xanthopterin (XPT), an unconjugated pteridine compound, affects cell growth and differentiation. When injected into rats, XPT has caused changes that have been interpreted as renal growth and hypertrophy. In the present study, we investigated the effect of intraperitoneal administration of XPT on the renal function in the rat. XPT administration was associated with polyuria and a reversible form of nonoliguric acute renal failure (ARF), with renal function declining maximally after 2 days and returning to normal after 7 days. The polyuria was due, at least in part, to a concentrating defect that was vasopressin resistant. The ability of XPT to induce ARF was modulated by dietary salt intake, being enhanced by a low-sodium diet and prevented by a high sodium intake. Histological examination of the kidneys showed intratubular crystal deposition and acute tubule necrosis, suggesting that XPT induces crystal nephropathy. There was an increase in wet and dry weights of the kidney and an increased DNA/protein ratio, compatible with a hyperplastic response. Because the severity of other crystal nephropathies may be modulated by urine flow rate and pH, we studied the ability of water diuresis or alkaline diuresis to protect against XPT-induced ARF. Both water diuresis and HCO3 loading blunted the ability of XPT to decrease renal function. The change in renal function induced by XPT in the various groups was paralleled by corresponding changes in the levels of XPT-like substances in the kidney and by the amount of crystal deposition. Thus, XPT injection induces crystal nephropathy, the severity of which can be modulated by dietary salt intake, urine pH, and urine flow rate.
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PMID:Xanthopterin-induced renal dysfunction: a reversible model of crystal nephropathy. 789 1

To examine the mechanisms of cell volume regulation in response to hyperosmolality, segments of the inner stripe of rabbit outer medullary collecting duct (OMCDi) were perfused in vitro. The cross-sectional area of the tubule was monitored as an index of the relative cell volume. When luminal and basolateral osmolalities were increased from 290 to 390 mOsm simultaneously, the tubule cell shrank instantaneously and reswelled gradually, showing the so-called regulatory volume increase (RVI). Basolateral Na+ removal and addition of basolateral ethyl isopropyl amiloride (EIPA) decreased the RVI response by 76 and 66%, respectively. By contrast, apical Na+ removal had no effect on this response. RVI response was also inhibited by basolateral, but not luminal, Cl- removal (-63%), by total HCO3- removal (-74%), and by adding basolateral 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (-62%). Intracellular pH did not change significantly during RVI. Vasopressin increased RVI response by 56%. However, this increase was abolished in the absence of basolateral Na+ and Cl-, and in the presence of basolateral EIPA and DIDS. These results suggest that major mechanisms responsible for RVI are Na(+)-H+ and Cl(-)-HCO3- exchange systems in the basolateral membrane, and that these systems are stimulated by vasopressin in rabbit OMCDi.
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PMID:Mechanisms of regulatory volume increase in collecting duct cells. 800 44


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