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)

Uptake of arginine-vasopressin, VP, at the luminal side of the blood-brain barrier (BBB) was studied by means of an in situ brain perfusion technique in the guinea-pig. Kinetic experiments revealed a saturable peptide influx into the parietal cortex, caudate nucleus and hippocampus with Km between 2.1 and 2.7 microM, and Vmax ranging from 4.9 to 5.6 pmol.min-1.g-1. The non-saturable component, Kd, was not significantly different from zero. Influx of VP into the brain was not altered by the presence of the peptide fragments: VP-(1-8), pressinoic acid and [pGlu4,Cyt6]VP-(4-9) at 4.5 microM, nor yet by the aminopeptidase inhibitor, bestatin (0.5 mM) and the L-amino acid transport system substrates, L-tyrosine and L-phenylalanine at 5 mM. At a perfusate concentration of 4.5 microM, the V1-vasopressinergic receptor antagonist, d(CH2)5[Tyr(Me)2]VP, reduced VP influx; regional Ki values, assuming that the observed inhibitions were purely competitive, ranged between 4.7 and 8.5 microM. It is concluded that there is an apparent cerebrovascular permeability to circulating VP due to the presence of a carrier-mediated transport system for the peptide located at the luminal side. The mechanism for VP BBB uptake exhibits no affinity for peptide fragments and large neutral amino acids, but requires reception of the intact molecule, which may be the same initial step for both the BBB VP transporter and the V1-receptor.
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PMID:Kinetics of arginine-vasopressin uptake at the blood-brain barrier. 236 78

As part of a program aimed at designing more potent and selective antagonists of the antidiuretic responses to arginine-vasopressin (AVP), we substituted O-alkyl-D-tyrosine (where alkyl = methyl, ethyl, isopropyl, or n-propyl) at position 2 in our eight previously reported O-alkyl-L-tyrosine antagonists of antidiuretic and vasopressor responses to AVP. We also substituted D-tyrosine for L-tyrosine in two vasopressor antagonists with weak antidiuretic agonistic activity, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),4-valine,8-D-arginine]vasopressin [d(CH2)5VDAVP] and its L-arginine isomer [d(CH2)5VAVP]. The ten analogues, synthesized by the solid-phase method, are as follows: 1, d(CH2)5-D-Tyr(Me)VDAVP; 2, d(CH2)5-D-Tyr(Et)VDAVP; 3, d(CH2)5-D-Tyr(i-Pr)VDAVP; 4, d(CH2)5-D-Tyr(n-Pr)VDAVP; 5, d(CH2)5-D-Tyr(Me)VAVP; 6, d(CH2)5-D-Tyr(Et)VAVP; 7, d(CH2)5-D-Tyr(n-Pr)VAVP; 8, d-(CH2)5-D-Tyr(i-PR)VAVP; 9, d(CH2)5-D-TyrVDAVP; 10, d(CH2)5-D-TyrVAVP. These analogues were tested for agonistic and antagonistic activities in rat antidiuretic and rat vasopressor systems. All ten D-tyrosine analogues possess transient weak antidiuretic activities (0.004--0.05 U/mg). Subsequent doses of AVP are reversibly antagonized for 1--3 h, depending on the dose of the antagonist. They exhibit the following antiantidiuretic pA2 values: 1, 7.19 +/- 0.11; 2, 7.59 +/- 0.04; 3, 7.51 +/- 0.06; 4, 7.60 +/- 0.05; 5, 7.77 +/- 0.07; 6, 7.81 +/- 0.07; 7, 7.66 +/- 0.11; 8, 7.61 +/- 0.06; 9, 7.03 +/- 0.05; 10, 7.51 +/- 0.08. They are all effective antagonists of vasopressor responses to AVP. Analogues 1--8 are two to ten times more potent than their respective O-alkyl-L-tyrosine isomers as antidiuretic antagonists. Since the vasopressor potencies of the O-alkyl-L-tyrosine analogues have either diminished or remained virtually unchanged, these analogues exhibit a selective increase in their antiantidiuretic/antivasopressor ratios with respect to their respective O-alkyl-L-tyrosine analogues. The finding that the substitution of an unalkylated D-tyrosine for L-tyrosine in d(CH2)5VDAVP and d(CH2)5VAVP converts these weak antidiuretic agonists into potent antagonists of antidiuretic responses to AVP is highly significant, especially in view of the relative ease of synthesis and much higher yields of unalkylated vs. alkylated tyrosine analogues. These ten new analogues are potentially useful as pharmacological tools and as therapeutic agents. The findings presented here have also obvious potential for the design of even more potent and selective antidiuretic antagonists.
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PMID:Design of more potent antagonists of the antidiuretic responses to arginine-vasopressin. 708 21

In this work, Raman spectroscopy (RS) was employed to characterize molecular structures of [Arg8]vasopressin (AVP) and its [Acc2,D-Arg8]AVP, [Acc3]AVP, and [Cpa1, Acc3]AVP analogues. The RS band assignments have been proposed. To determine the mechanism of adsorption of the above-mentioned compounds adsorbed on a colloidal silver surface, surface-enhanced Raman spectra (SERS) were measured. The SERS spectra were used to determine relative proximity of the adsorbed functional groups of [corrected] investigated peptides and their orientation on the silver surface. The AVP and [Acc3]AVP SERS spectra (Acc: 1-aminocyclohexane-1-carboxylic acid) show that the L-tyrosine (Tyr) lies far from the metal surface, whereas the [Cpa1,Acc3]AVP spectrum (Cpa: 1-mercaptocyclohexaneacetic acid) provides evidence that Tyr interacts with the silver surface. These results suggest that [corrected] the binding of the Tyr-ionized phenolic group might be responsible for the selectivity of the analogues. We show that the aromatic ring of L-phenylalanine (Phe) of AVP and [Acc2,D-Arg8]AVP interacts with the silver surface. The strength of this interaction is considerably weaker for [Acc2,D-Arg8]AVP than for AVP. This might be due either to a longer distance between the Phe ring and the silver surface, or to the almost perpendicular orientation of the Phe ring towards the surface. The carbonyl group of the L-glutamine [corrected] (Gln) or L-asparagine [corrected](Asn) of AVP, [Acc2,D-Arg8]AVP, and [Acc3]AVP is strongly bound to the silver surface. We have also found that all peptides adsorb on the silver surface via sulfur atoms of the disulfide bridge, adopting a "GGG" conformation, except [Cpa1,Acc3]AVP, which accepts a "TGG" geometry.
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PMID:Raman and surface-enhanced Raman spectroscopy investigation of vasopressin analogues containing 1-aminocyclohexane-1-carboxylic acid residue. 1674 75