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)

[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin was prepared from beta-Mpa(beta-(CH2)5)(Bzl)-Tyr(Bzl)-Ile-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by removal of the Bzl-protecting groups with Na-NH3 followed by cyclization of the resulting disulfhydryl compound with K3Fe(CN)6.The analog was purified by desalting on Sephadex G-15 in 50% HOAc and gel filtration on Sephadex G-25 and LH-20. The protected intermediate above was synthesized from Z-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwose p-nitrophenyl ester method using Nalpha-Boc protection at the penta-, hexa-, and octapeptide stages. The analog was found to be a potent inhibitor of the oxytocic and avian vasodepressor effects of oxytocin (pA2 values of 7.43 and 8.30, respectively) but was only a weak inhibitor of the rat pressor effect of 8-lysine-vasopressin. The rat antipressor potency of [1-deaminopenicillamine]oxytocin was also determined in this study: pA2 = 6.27. Of the alkyl-substituted 1-position analogs of oxytocin studied so far, [1-beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin is the most potent antioxytocic agent.
 ...
PMID:[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin, a potent inhibitor of oxytocin. 113 19

[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

[3-beta-(2-Thienyl)-L-alanine]-8-lysine-vasopressin was synthesized by solution techniques. The partially protected heptapeptide Boc-Cys(Ec)-Tyr-Thi-Gln-Asn-Cys(Ec)-Pro (1) was synthesized in a stepwise manner using the active ester method or the dicyclohexylcarbodiimide (DCC) coupling technique mediated by 1-hydroxybenzotriazole (HBt). The protected nonapeptide amide Boc-Cys(Ec)-Tyr-Thi-Gin-Asn-Cys(Ec)-Pro-Lys(Coc)-Gly-NH2 (2) was prepared by coupling 1 with Lys(Coc)-Gly-NH2 using DCC-HBt. From 2, [3-thienylalanine]-8-lysine-vasopressin was obtained by removing the Boc-protecting groups with trifluoroacetic acid and ethylcarbamoyl (Ec) protecting groups in refluxing liquid NH3 followed by oxidative cyclization in H2O-MeOH using ICH2CH2I. Purification was effected by partition chromatography followed by gel filtration. The highly purified product possesses activities in the oxytocic, avian vasodepressor, rat pressor, and antidiuretic assays of 19.0 +/- 0.5, 87 +/- 4, 243 +/- 5, and 332 +/- 32 units/mg, respectively. Thus [3-thienylalanine]-8-lysine-vasopressin has higher oxytocic, avian vasodepressor, and antidiuretic potencies than does 8-lysine-vasopressin, whereas its pressor potency is about the same as or slightly lower than that of 8-lysine-vasopressin.
 ...
PMID:Synthesis and some pharmacological properties of (3-beta-(2-thienyl)-L-alanine)-8-lysine-vasopressin. 117 84

The role of plasma membrane fluidity in the regulation of kidney tubule water permeability has been uncertain. We have used new methods to image the fluorescence anisotropy of fluidity-sensitive fluorophores (Fushimi, Dix, and Verkman. Biophys. J. 57: 241-254, 1990) to quantitate membrane fluidity in cells of the vasopressin-sensitive cortical collecting tubule (CCT) and water-impermeable cortical thick ascending limb (CTAL). Isolated tubule segments from rabbit kidney were perfused in vitro, and apical or basolateral plasma membranes were stained with trimethylammonium diphenylhexatriene (TMA-DPH). TMA-DPH anisotropy (r) was imaged quantitatively by an epifluorescence microscope equipped with rotatable polarizers; TMA-DPH nanosecond lifetime (tau) was measured by flash-lamp excitation and gated photomultiplier detection. In CCT, apical membrane r (0.254 +/- 0.003) was similar to basolateral r (0.252 +/- 0.005). Serosal vasopressin at a dose that increased water permeability greater than 10-fold (250 microU/ml) did not affect apical membrane r (delta r = 0.002 +/- 0.003; 7 tubules). A 0.002 change in r was less than that produced by a 2 degrees C temperature variation. In CTAL, apical membrane r was 0.249 +/- 0.002, similar to r from basolateral membrane of proximal tubule (0.24), but much less than that of proximal tubule apical membrane (0.29). These results establish methodology to quantitate fluidity in intact kidney tubule segments and provide the first measurements of plasma membrane fluidity in CTAL and CCT. Our results suggest that regulation of bulk membrane fluidity in CCT apical membrane is not a component of the hydrosmotic action of vasopressin and that low apical membrane fluidity is not responsible for the low water and NH3 permeabilities in CTAL.
 ...
PMID:Relationship between vasopressin-sensitive water transport and plasma membrane fluidity in kidney collecting tubule. 198 73

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)
 ...
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

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)
 ...
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