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Biomedical subjects

R Walter

Publications and source records attributed to R Walter.

At least 235 records · Page 13Linked to original sources
PubMed1975

Neurohypophyseal hormones, analogs, and fragments: their effect on puromycin-induced amnesia.

Neurohypophyseal hormones and several of their analogs, as well as N-terminal and C-terminal fragments, have been studied for their ability to attenuate puromycin-induced amnesia in mice. [8-Lysine]vasopressin, [8-arginine]vasopressin, and the analogs des-9-glycinamide-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-lysine]vasopressin, [1,6-aminosuberic acid, 8-lysine]vasopressin, [4-leucine, 8-lysine]vasopressin, glycyl-glycyl-glycyl-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-D-arginine]vasopressin, and [1,6-aminosuberic acid, 8-arginine]vasopressin are active. [8-Arginine]oxytocin as well as oxytocin and all of its other analogs tested are inactive with the striking exception of glycyl-glycyl-glycyl-oxytocin. The structural aspects of the neurohypophyseal hormones which appear to be important for significant activity in memory consolidation include the combination of a cyclic moiety containing the Tyr and Phe residues along with a basic residue in position 8. Another series of active compounds comprises C-terminal neurohypophyseal peptides and analogs thereof, including the naturally occurring Pro-Leu-Gly-NH2 and, most surprisingly, Leu-Gly-NH2, as well as its derivatives D-Leu-Gly-NH2 and the diketopiperazine, cyclo(-Leu-Gly-).

Amnesia↗
PubMed1975

Oxytocin analogs with substitutions in postions 3 and 4.

Synthesis and biological properties are reported for some analogs of oxytocin with replacements of the isoleucine residue in position 3, i.e., (3-proline)oxytocin and(3-D-alanine)oxytocin, and the glutamine residue in position 4, i.e., (4-D-alanine)-oxytocin and (4-D-leucin)oxytocin. (3-Proline)oxytocin exhibited smaller than0.02 U/MG oxytocic activity, 0.005 plus or minus smaller than 0.001 U/mg rat pressor activity and 0.003 plus or minus 0.0001 U/mg antidiuretic activity. (3-D-Alanine)oxytocin had no agonistic activity in the bioassays tested except for the rat antidiuretic assay (smaller than 0.0005 U/mg). The 4-D-alanine analog showed 0.05 plus or minus 0.003 U/mg oxytocic activity, 0.07 plus or minus 0.01 U/mg avian vasodepressor activity, and smaller than 0.001 U/mg rat antidiuretic activity. (4-D-Leucine)oxytocin possessed 0.001 plus or minus U/mg rat pressor activity, and showed slight inhibitory properties in the oxytocic and avian vasodepressor assays, inhibiting the oxytocin response in the latter assay by about 60% at a girnibe-to-analog ratio of 1:5000. The activity profiles of the analogs are compared to that of oxytocin and are discussed on the basis of the proposed solution conformation of oxytocin.

Alanine↗
PubMed1975

Differences in the enzymatic inactivation of arginine vasopressin and oxytocin by rat kidney homogenate.

Arginine-vasopressin and oxytocin, both 14C-labeled in the glycine residue, are enzymatically inactivated by rat kidney supernatant. Production of radioactive metabolites of each hormone was followed as a function of time. Both oxytocin and vasopressin are degraded by an enzyme which cleaves their Pro-X bonds, to release Leu-Gly-NH2 from oxytocin and Arg-Gly-NH2 from vasopressin. In addition, oxytocin alone is degraded rapidly by a chymotrypsin-like enzyme which directly releases Gly-NH2 from the hormone. The direct release of Gly-NH2 from vasopressin in the homogenate is of minor importance, but there occurs a transient formation of an uncharacterized fragment in significant amounts. The data are interpreted to indicate that the difference in the overall mechanism of inactivation of the two hormones by the rat kidney extract is a result of the high level of the enzymic activity which releases Gly-NH2 directly from oxytocin, compared to the low level of activity releasing Gly-NH2 directly from the antidiuretic hormone. This allows, in the case of arginine vasopressin, a greater expression of the activity of enzyme(s) giving rise to uncharacterized fragment(s) and of the Pro-X cleaving enzyme.

Arginine↗
PubMed1975

Significant differences in the degradation of pro-leu-gly-nH2 by human serum and that of other species (38484).

The acyclic C-terminal tripeptide of oxytocin, H-Pro-Leu-Gly-NH-2, is not degraded upon incubation with human (male,female or pregnant female) plasma or serum for 1hr at 37 degrees. However, the sera of other species tested, including rat, chicken and carp, degrade this tripeptide 100%, 4% and 30%, respectively, in 1 hr, as determined by quantitative amino acid analysis of released products. Among the species studied there seems to exist a correlation between the anatomic development of the pars intermedia and the ability of the serum to hydrolyze H-Pro-Leu-Gly-NH-2, which has been proposed to be a MSH-release-inhibiting factor. The only identified degradation products are Pro, Leu and H-Gly-NH-2 with no detectable levels of H-Leu-Gly-NH2. The dipeptides H-Leu-Gly-NH-2 and H-Pro-Leu-OH are each cleaved at similiar rates in either human or rat serum, although the rate of hydrolysis of both peptides is lower in human than in rat. Thus, it does not appear that the dipeptide, H-EU-Gly-NH-2, can accumulate as one of the breakdown products of the tripeptide. The arylamidase present in rat serum has different characteristics from the enzyme in rat brain which can degrade H-Pro-Leu-Gly-NH-2.

Aminopeptidases↗
PubMed1974

Conformational studies on arginine vasopressin and arginine vasotocin by proton magnetic resonance spectroscopy.

The assignments and partial conformational analysis of the 220-MHz (1)H nuclear magnetic resonance spectrum of the neurohypophyseal hormones arginine vasopressin and arginine vasotocin in uniformaly deuterated dimethylsulfoxide are reported. The chemical shifts, vicinal coupling constants, temperature coefficients of chemical shifts, and proton-deuterium exchange rates for protons of arginine vasopressin and arginine vasotocin are compared with those for the corresponding protons of the related neurohypophyseal hormones lysine vasopressin and oxytocin. Although to a first approximation the backbone conformations of the hormones exhibit conformational similarities, spectral differences are seen for protons in the amino acid residues that comprise the 20-membered ring moieties. It is inferred that there is a gradual shift in the average conformation in going from arginine vasopressin and lysine vasopressin via arginine vasotocin to oxytocin. As judged on the basis of earlier studies, it is evident that the C-terminal acyclic tail moiety exhibits an enhanced mobility over that of the ring moiety in all of the neurohypophyseal hormones studied and, moreover, that this motion is greater in arginine vasopressin and arginine vasotocin than in oxytocin.

Arginine↗
PubMed1974

Long-range, pH-dependent effects on the carbon-13 nuclear magnetic resonance spectra of oxytocin.

The effects of hydrogen ion concentrations on the carbon-13 nuclear magnetic resonance spectra of oxytocin were investigated. The starting pD of 3.0 was increased stepwise to 8.4. A change of the state of protonation of the N-terminal amino group of oxytocin is accompanied by changes in chemical shifts of carbon-13 nuclei of amino-acid residues located in the 20-membered ring of the hormone. The resonance positions of the acyclic peptide portion, Pro-Leu-Gly-NH(2), remain constant. The pD-induced chemical-shift changes of carbons up to five bonds removed from the site of protonation are interpreted in terms of "through-bond" and "through-space" mechanisms. Chemical-shift changes of carbons more than five bonds removed are proposed to have a conformational origin. It is suggested that a change in the charge density of the amino group perturbs the dihedral angle of the -CH(2)-S-S-CH(2)- moiety of oxytocin, which in turn significantly affects the overall conformation of the 20-membered ring of the hormone.

Carbon Isotopes↗