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)

The role of N-glycosylation in the function and biosynthesis of the vasopressin V2-receptor in LLC-PK1 renal epithelial cells was examined using various lectins and inhibitors operating at different steps of the glycosidic pathway. Tunicamycin, which blocks all N-glycosylation, and castanospermine, which inhibits glycosidase I and hence blocks formation of high-mannose-type N-glycosylated intermediates, resembled one another in affecting V2-receptor biosynthesis and internalization in a concentration-dependent manner. In contrast, swainsonine, an inhibitor of mannosidase II and hence of complex-type oligosaccharide formation, had no effect. Interestingly, the alpha-D-mannose/alpha-D-glucose-specific lectin concanavalin A, (Con A), in contrast to the beta-D-galactose-specific lectin ricin, had a marked effect on the V2-receptor in LLC-PK1 cells, increasing both receptor numbers up to twofold in vivo and specific [3H]AVP binding up to 50% in vitro in a concentration-dependent manner. The concentrations inducing half-maximal response were about 0.2 and 20 micrograms/ml for the in vivo and in vitro responses, respectively, implying distinct effects on V2-expression and ligand binding. That the in vitro effect on binding was due to a direct effect on the V2-receptor could be shown by the lack of a Con A effect on [3H]AVP binding in membranes prepared from LLC-PK1 cells down-regulated for the V2-receptor or from cells of the LLC-PK1 V2-receptor deficient mutant M18. All results were consistent with a functional role for N-glycosylation of the V2-receptor in LLC-PK1 cells.
 ...
PMID:N-glycosylation plays a role in biosynthesis and internalization of the adenylate cyclase stimulating vasopressin V2-receptor of LLC-PK1 renal epithelial cells: an effect of concanavalin A on binding and expression. 153 96

Three clones of the pig kidney cell line LLC-PK1 were isolated and characterized with regard to morphology, growth, proximal tubule enzyme activity, sugar uptake capacity, and hormone and drug responsiveness in a defined medium. Clone N4 was similar in morphology to the wild type (WT), whereas clone F8 showed loose attachment to the substrate, formed large, sweeping domes, and had an elongated desmosome junction between cells. The third clone, F2, did not form domes and showed a marked reduction in growth rate. Cultures of WT, N4, and F8 had higher specific activities of the enzyme alkaline phosphatase and gamma-glutamyl transpeptidase at confluence relative to growing cells; however, there was no evidence of an increase in activity of either enzyme at confluence in F2. Phlorizin-sensitive alpha-methyl-D-glucoside uptake and cytochalasin B-sensitive 2-deoxy-D-glucose uptake were measured in confluent cultures grown on porous filter supports. None of the clones lacked either of the hexose transport systems, although quantitative differences were evident. N4 cells grown in a defined medium in 96-well culture plates were tested in situ for their enzyme responses to differentiation inducers, tumor promoters, and hormones. Alkaline phosphatase activity was significantly increased at confluence by serum, parathyroid hormone (PTH), and vasopressin (AVP), and was decreased by tetradecanoylphorbol acetate (TPA) and epinephrine (EPI). Glutamyl transpeptidase activity was decreased at confluence by serum, TPA, and EPI. Similar tests on alpha-methyl-D-glucoside uptake showed that serum, TPA, PTH, and AVP had no significant effect on phlorizin-sensitive uptake; however, calcitonin increased uptake by 84% (n = 18). It was concluded that LLC-PK1 clones maintained in a defined medium are useful models for studying renal cell function.
 ...
PMID:Growth, enzyme activity, sugar transport, and hormone supplement responses in cells cloned from a pig kidney cell line LLC-PK1. 256 38

1. The specificity of the effect of glucose on the induction of glucokinase activity that occurs when hepatocytes freshly isolated from 13-day-old rats are incubated in Medium 199 together with insulin [Wakelam & Walker (1980) FEBS Lett. 111, 115-119] was examined. A pattern that is different from other known effects of glucose is found, and metabolism of this compound is not necessarily to account for this particular effect. 2. The effects of a raised glucose concentration and of insulin on the induction can be separated. The hexose initiates the process in the absence of insulin in a manner that is sensitive to actinomycin D but not to cycloheximide. The subsequent effect of insulin is dependent on the prior effect of glucose or other positive analogue, does not require the presence of glucose and is inhibited by cycloheximide but not by actinomycin D. 3. Induction of glucokinase in vitro in hepatocytes from neonatal animals is inhibited by adrenaline, glucagon and dibutyryl cyclic AMP, but not by vasopressin or angiotensin II. The inhibition by cyclic AMP is on the stage requiring insulin and is comparatively specific, because total protein synthesis is not apparently diminished. 4. The implications of these results are discussed with reference to possible mechanisms of induction and to the situation in vivo.
 ...
PMID:The separate roles of glucose and insulin in the induction of glucokinase in hepatocytes isolated from neonatal rats. 627 13

Vasopressin, phenylephrine, and A23187 cause an accumulation of fructose 2,6-bisphosphate in hepatocytes from fed rats, but not in Ca2+-depleted hepatocytes from fed rats or in phosphorylase kinase-deficient hepatocytes from (gsd/gsd) rats. The effect of vasopressin and phenylephrine is not found in hepatocytes from overnight-starved rats. Thus, the accumulation of fructose 2,6-bisphosphate by these agents may depend on the stimulation of glycogenolysis and on the resulting accumulation of hexose 6-phosphate. In support of this hypothesis, conditions are described for the enzymatic synthesis of fructose 2,6-bisphosphate from fructose 6-phosphate and Mg-ATP in liver extracts. Half-maximal activity (0.8 nmol/min.g) is obtained with about 60 microM fructose 6-phosphate, and the activity can be separated fom phosphofructokinase by ammonium sulfate fractionation. Treatment of rats or isolated hepatocytes with glucagon results in a 4-5-fold decrease in the maximal activity of this enzyme.
 ...
PMID:Fructose 2,6-bisphosphate. Hormonal regulation and mechanism of its formation in liver. 679 May 47

1. The effects of hyponatraemia on cerebral blood flow, oxidative metabolism, and transfer of Na and K from the brain--c.s.f. compartment to blood have been examined in anaesthetized calves 2--6 weeks after birth. 2. Dilutional hyponatraemia was produced by administration of a long-acting antidiuretic hormone analogue (desmopressin) and the infusion of hexose solutions of various concentrations. Cerebral blood flow was measured using a hydrogen clearance technique, and metabolism and cation transfer quantified by simultaneous determination of arterio-cerebral venous concentration differences. 3. Sustained hyposmolar hyponatraemia (plasma osmolality, 232 +/- 1 m-osmole/kg; plasma Na, 117 . 1 +/- 0 . 5 m-mole/l.) was associated with a fall in cerebral blood flow, and increase in measured net transfer of K from the brain-c.s.f. compartment to the circulation. C.s.f. Na concentration and osmolality were both decreased. 4. No alterations in these variables occurred during sustained isosmolar hyponatraemia (plasma osmolality, 284 +/- 2 m-osmole/kg; plasma Na, 119 . 9 +/- 0 . 2 m-mole/l). 5. The results are discussed in relation to the route, mechanism and time course of K loss from brain during hyponatraemia.
 ...
PMID:Potassium transfer from brain to blood during sustained hyponatraemia in the calf. 746 70

The purpose of this study was to identify the mechanism by which proglycosyn and resorcinol decrease the phosphorylase a content and the fructose 2,6-bisphosphate concentration in isolated hepatocytes. The intracellular concentrations of the glucuronide derivatives of proglycosyn and resorcinol have been measured by HPLC in hepatocytes incubated for 5 min or 30 min with different concentrations of these agents. At both times, there was a reciprocal relationship between the phosphorylase a content and the intracellular concentration of the glucuronidated metabolites, half-maximal inactivation being observed at about 2 mumol/g protein and 0.25 mumol/g protein for resorcinylglucuronide and proglycosyn-glucuronide, respectively. Glycogen synthase was not significantly activated by these agents after 5 min but was well activated after 30 min. Preincubation of hepatocytes with 1 mM resorcinol or with 100 microM proglycosyn resulted in a decrease in the rate at which phosphorylase was activated following the addition of glucagon, vasopressin, the protein phosphatase inhibitor calyculin A or the calcium ionophore A 23187, but did not reduce the rate of synthase inactivation. Proglycosynglucuronide and resorcinylglucuronide inhibited phosphorylase kinase in liver Sephadex filtrates, with Ki values of about 0.75 mM and 4 mM, respectively. Preincubation of the filtrates with ATP and cAMP decreased the sensitivity of phosphorylase kinase to resorcinylglucuronide by about fourfold. It is concluded that the effect of resorcinol and proglycosyn on the phosphorylase a content is due, at least partly, to an inhibition of phosphorylase kinase by their glucuronidated metabolites. Resorcinol and proglycosyn caused a parallel decrease in the concentration of fructose 2,6-bisphosphate and of hexose 6-phosphates, without significantly changing the activity of 6-phosphofructo-2-kinase. The decrease in the fructose 2,6-bisphosphate concentration appears therefore to be secondary to the decrease in the hexose 6-phosphate concentration.
 ...
PMID:Involvement of phosphorylase kinase inhibition in the effect of resorcinol and proglycosyn on glycogen metabolism in the liver. 852 56

To extend the utility of a renal targeting system using carbohydrate derivatives, we investigated the in vivo tissue distribution in rats of arginine-vasopressin (AVP) derivatives modified at the phenolic hydroxy group of tyrosine by linking it to some sugars, namely D-glucose, D-galactose, D-mannose and L-fucose, via an octamethylene group. The glycosyl and mannosyl derivatives of AVP exhibit renal-selective distribution in vivo. In addition, the glucosyl and mannosyl derivatives exhibited specific binding to the kidney microsomal fraction in vitro. Modification with D-glucose or D-mannose at the tyrosine side chain is a suitable methodology for renal targeting, as well as at N-terminal amine.
 ...
PMID:Renal targeting of arginine-vasopressin by modification with carbohydrates at the tyrosine side chain. 1054 62