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)

[4-Phenylalanine]oxytocin was prepared from Z-Cys(Bzl)-Tyr(Bzl)-Ile-Phe-Asn-Cys(Bzl)-Pro-Leu-Gly-NG2 (4) by deprotection with Na in NH3 followed by cyclization of the resulting disulfhydryl compound with ICH2CH2I. The protected peptide 4 was prepared from Boc-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwise solution method. Coupling was effected by a modification of the dicyclohexylcarbodiimide-1-hydroxybenzotriazole preactivation method wherein the precipitate of dicyclohexylurea is removed by filtration prior to mixing of the amino and carboxyl components. The analog was found to be an effective inhibitor of the antidiuretic (ADH) response to exogenous arginine-vasopressin. It produced marked diuresis in the anti-ADH assay at approximately the same dose level as does [Leu4]oxytocin but, in contrast to [Leu4]oxytocin, showed natriuretic activity only at relatively high dose levels. In addition, [Phe4]oxytocin exhibited 0.15% of the oxytocic potency of oxytocin, weak antiavian vasodepressor activity (pA2 = 6.93), and no measurable rat pressor activity.
 ...
PMID:(4-Phenylalanine)oxytocin, an inhibitor of the antidiuretic effect of 8-arginine-vasopressin. 115 80

The state of phosphorylation of phenylalanine hydroxylase was determined in isolated intact rat hepatocytes. 32P-labeled phenylalanine hydroxylase was immunoisolated from cells loaded with 32Pi or from cell extracts 'back-phosphorylated' with [gamma-32P]ATP by cAMP-dependent protein kinase. The rate of phenylalanine hydroxylase phosphorylation in cells with elevated cAMP was similar to that observed for the isolated enzyme phosphorylated by homogeneous cAMP-dependent protein kinase. The phosphorylation rate in cAMP-stimulated cells was increased up to four times (reaching 0.018 s-1) by the presence of phenylalanine, the phosphate content (mol/mol hydroxylase) increasing to 0.5 from the basal level (0.17) in 50 s. The half maximal effect of phenylalanine was obtained at a physiologically relevant concentration (110 microM). The synthetic phenylalanine hydroxylase cofactor dimethyltetrahydropterin also enhanced the cAMP-stimulated phosphorylation of phenylalanine hydroxylase, presumably by displacing the endogenous cofactor, tetrahydrobiopterin. Phenylalanine was a negative modulator of the phosphorylation of phenylalanine hydroxylase induced by incubating cells with vasopressin or with the phosphatase inhibitor okadaic acid. The same site on the phenylalanine hydroxylase was phosphorylated in response to these two agents as in response to elevated cAMP. The available evidence suggested that not only vasopressin, but also okadaic acid, acted by stimulating the multifunctional Ca2+/calmodulin-dependent protein kinase II or a kinase with closely resembling properties.
 ...
PMID:Phenylalanine positively modulates the cAMP-dependent phosphorylation and negatively modulates the vasopressin-induced and okadaic-acid-induced phosphorylation of phenylalanine 4-monooxygenase in intact rat hepatocytes. 131 38

Desmopressin [1-(mercaptopropanoic acid)-8-D-arginine vasopressin; dDAVP] is a vasopressin analogue with a selective antidiuretic effect. The oral bioavailability of desmopressin is limited due both to its high hydrophilicity leading to a low intestinal permeability and to low enzymatic stability. The degradation of desmopressin was investigated in aqueous buffer solutions (pH 6.00-9.00) containing the enzyme alpha-chymotrypsin at a concentration of 0.50 mg/ml at 37 degrees C. The degradation of desmopressin was also studied in solutions containing alpha-chymotrypsin in the concentration range 0.10-1.00 mg/ml (pH 7.40 and 37 degrees C). The rate of degradation was shown to be highly dependent on both enzyme concentration and pH. Maximal alpha-chymotrypsin activity was observed in the pH range 7.40-8.00. It was observed that phenylalanine was formed during the degradation of desmopressin. Phenylalanine was formed in the amount of 20% in 120 min. In the same time period 95% of desmopressin was degraded. The formation of phenylalanine can be explained from the substrate specificity of alpha-chymotrypsin. Cyclodextrins are known to stabilize drugs including peptides against both chemical and enzymatic degradation. In this study it was shown that hydroxypropyl cyclodextrins (alpha, beta and gamma) stabilized desmopressin against alpha-chymotrypsin-catalyzed degradation. The stabilization was by a factor of 3, 9 and 8 at the concentration 12.5% (w/v) for hydroxypropyl-alpha-cyclodextrin, hydroxylpropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin.
 ...
PMID:alpha-Chymotrypsin-catalyzed degradation of desmopressin (dDAVP): influence of pH, concentration and various cyclodextrins. 1020 42