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At least 19 recordsLinked to original sources
PubMed1976

Solid phase synthesis and some pharmacological properties of 8-D-homoarginine-vasopressin and 1-deamino-8-D-homoarginine-vasopressin.

Fully protected 8-D-lysine-vasopresin and 1-deamino-8-D-lysine-vasopressin were synthesized by the solid phase method. Selective removal of the lysine protection and reaction with 1-guanyl-3,5-dimethylpyrazole converted D-lysine into D-homoarginine. The title compounds were then obtained by treatment with sodium in liquid ammonia and oxidation in dilute aqueous solution. Although the antidiuretic activities are lower than for the corresponding D-argining derivatives, the even lower pressor effects make the new analogues highly specific antidiuretic agents. The A/P ratios for 8-D-homoarginine-vasopressin and its 1-deamino derivative are 100 and 3,300, respectively.

Animals↗
PubMed1977

Solid phase synthesis and some hormonal activities of 8-L-homoarginine-vasotocin and 1-deamino-8-L-homoarginine-vasotocin.

8-L-Homoarginine-vasotocin and its 1-deamino derivative were synthesized by the solid phase method. Both compounds possessed high activities in the uterus contraction and fowl depressor assays and showed higher pressor activities than the corresponding vasopressins. Homoarginine-vasotocin, unexpectedly, was a more potent antidiuretic agent than its deamino analogue.

Amino Acid Sequence↗
PubMed1984

Comparison of the antinociceptive effect between the cyclic dipeptide cyclo[Tyr(Et)-homoarginine] and the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe in rats.

The antinociceptive effect of the cyclic dipeptide cyclo[Tyr(Et)- homoarginine] (C.TEHA) was examined utilizing the tail flick test and the digitus pinching test in rats in comparison with the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe (B.TEHM). Though both dipeptides administered into the lateral, 3rd and 4th cerebroventricles produced antinociceptive effects equipotent to morphine, except for the 4th cerebroventricular administration of B.TEHM, the administration into the spinal subarachnoid space was without effect. The effect of B.TEHM was completely antagonized by the pretreatment of naloxone (i.p.) when administered into the 3rd cerebroventricle where its effect was demonstrated to be the most potent. However, naloxone had no significant effect on C.TEHA administered into the 3rd cerebroventricle in both tests. It was concluded that both dipeptides act on the upper brain stem, especially around the 3rd cerebroventricle. Moreover, it was also thought that the effect of B.TEHM may be involved in the brain opioid system, and that of C.TEHA can be produced via a naloxone-resistant opioid system or a non-opioid system.

Analgesics↗
PubMed1997

Secretion of homoarginine into the gut of chickens.

A technique, based on the homoarginine present in guanidinated proteins, has been used to distinguish between endogenous secretions and exogenous dietary amino acids in the ileal digesta of monogastric animals. This technique assumes that the ingested homoarginine is not recycled into the small intestine after absorption, but this assumption is yet to be experimentally validated in chickens. The secretion of homoarginine into the gut of broilers that were intravenously infused with 20 and 40 mmol/L homoarginine solutions was assessed. The plasma concentrations of homoarginine increased with increasing concentrations of homoarginine infused. However, only negligible levels of homoarginine (7.0 to 45.2 micrograms/g dry matter) were found in the digesta. Less than 0.01% of the intravenously infused homoarginine was recovered in the intestinal digesta, indicating that the secretion of homoarginine into the gut of chickens was insignificant.

Amino Acids↗
PubMed1994

Sensitivity of intestinal alkaline phosphatase to L-homoarginine and its regulation by subunit-subunit interaction.

The inhibitory effect of levamisole and L-homoarginine on alkaline phosphatases (ALP, orthophosphoric monoester phosphohydrolase, EC. 3.1.3.1) in various tissues was studied to characterize differences in the mechanism of inhibition of ALP isoenzymes. The ALP activity from the placenta, kidneys, and a clonal osteogenic cell line, MC3T3-E1, was hyperbolically inhibited with a dependency on the concentration of levamisole (Ki0.5 = 10-12 microM) or L-homoarginine (Ki0.5 = 1 mM), but the activity of intestinal ALP was little inhibited by 240 microM levamisole and sigmoidally inhibited by L-homoarginine (Ki0.5 = 13 mM). Hill plot analysis of the L-homoarginine inhibition data showed that the Hill coefficient values of the placenta, kidney, and osteogenic cells were around 0.9-1.0 and that of the intestine was 1.8. The effect of sodium dodecyl sulfate (SDS), which may decrease the subunit-subunit interaction, on the L-homoarginine inhibition of the intestinal ALP was tested. The L-homoarginine concentration-dependent inhibition curve changed from sigmoidal to hyperbolic, and the Hill coefficients decreased with increasing concentrations of SDS. These results suggest that the differences in inhibition by L-homoarginine and affinity changes of intestinal ALP for L-homoarginine are caused by the subunit-subunit interaction of oligomers.

Alkaline Phosphatase↗
PubMed1982

Inhibitory effect of L-homoarginine on murine osteosarcoma cell proliferation.

An organ-specific alkaline phosphatase inhibitor, L-homoarginine, at 44.5 mM concentration inhibited [3H]thymidine uptake by C3H/He mouse osteosarcoma (OS) cells, while L-arginine, L-phenylalanine, and glycine had little effect on the uptake. This inhibitory effect of L-homoarginine persisted even after the cells were washed free of the amino acid with fresh media. L-Homoarginine did not affect [3H]thymidine uptake by mouse myeloma MOPC 104E cells. In long-term culture, 22.3 mM L-homoarginine inhibited proliferation of OS cells. L-Arginine at the same concentration inhibited the proliferation to a lesser extent. On the other hand, L-phenylalanine and glycine did not affect in vitro proliferation of OS cells. When the same number of viable OS cells was inoculated s.c. after culturing the 24 hr with 44.5 mM L-homoarginine or L-arginine, the tumor growth in mice given injections of L-homoarginine (but not L-arginine)-treated cells was delayed markedly. Electron microscopic studies indicated that the inhibiting effect on OS cell proliferation was associated with a marked increase in lysosomal granules and a decrease in virus-like structures. Similarly, biochemical assay for acid phosphatase of cell homogenates demonstrated a 2-fold increase of activity in L-homoarginine-treated cells when compared to controls and L-arginine-treated cells. Thus, L-homoarginine inhibits proliferation and alkaline phosphatase activity of mouse OS cells and appears to increase acid phosphatase activity in synthesis of lysosomal granules.

Alkaline Phosphatase↗
PubMed1982

[Inhibitory effect of L-homoarginine on murine osteosarcoma cell proliferation].

An organ-specific alkaline phosphatase (AIP) inhibitor, L-homoarginine at 44.5 mM concentration inhibited 3H-thymidine uptake by mouse C3H/He osteosarcoma (OS) cells, while L-arginine, L-phenylalanine and L-glycine had little effect on the uptake. This inhibitory effect by L-homoarginine persisted even after the cells were washed free of the amino acid with fresh media. L-homoarginine did not affect 3H-thymidine uptake by mouse myeloma MOPC 104E cells. In the long-term culture, 22.3 mM L-homoarginine inhibited proliferation of OS cells. L-Arginine at the same concentration inhibited the proliferation to a lesser extent. On the other hand, L-phenylalanine and L-glycine did not affect in vitro proliferation of OS cells. When similar numbers of viable OS cells were inoculated s. c. after culturing with 44.5 mM L-homoarginine or L-arginine for 24 hr, the tumor growth in mice injected with L-homoarginine (but not L-arginine) treated cells was delayed markedly. Electron microscopic studies indicated that the inhibitory effect on OS cell proliferation was associated with a marked increase in lysosomal granules and a decrease in virus-like structures. Similarly, a biochemical assay of acid phosphatase (AcP) of the cell homogenates demonstrated two-fold increase of the activity in L-homoarginine treated cells when compared to the controls and L-arginine treated cells. Thus, L-homoarginine inhibits proliferation and AIP activity of mouse OS cells and appears to promote cell differentiation as evidenced by the increased synthesis of cytoplasmic granules and acid phosphatase activity.

Alkaline Phosphatase↗
PubMed2003

L-homoarginine suppresses exocrine pancreas in rats.

Previously, we found that guanidinated casein, a L-homoarginine-containing protein, was a more potent stimulator of pancreatic enzyme secretion than intact casein in rats. In this study, we examined secretory response and adaptation of the exocrine pancreas to the administration of free L-homoarginine in normal and bile-pancreatic juice (BPJ)-diverted rats. An intraperitoneal injection of L-homoarginine (10 mg/rats) produced immediate and transient reduction in pancreatic secretion in BPJ-diverted rats, but not in normal rats. The BPJ-diverted rats were fed with either a 25% casein, 45% casein, or 45% casein diet supplemented with L-homoarginine (19 g/kg diet) for 4 days. Feeding of a diet containing L-homoarginine inhibited the pancreatic adaptation induced by the high-protein diet. These results indicate that L-homoarginine has an inhibitory effect on the secretion and production of exocrine pancreatic enzyme in BPJ-diverted rats, and L-homoarginine may have an antagonistic effect on CCK receptors.

Animals↗
PubMed1996

L-homoarginine studies provide insight into the antimetabolic properties of L-canavanine.

A method for the chemical synthesis of L-homoarginine, based on the guanidination of L-lysine with O-methylisourea, has been developed; this procedure provides radiochemically pure L-[guanidino-14C]homoarginine in high yield. Radiolabeled homoarginine is incorporated readily into the newly synthesized hemolymphic proteins of larvae of the tobacco hornworm, Manduca sexta without adversely affecting larval growth and development. This finding stands in sharp contrast to the effect of L-canavanine, another L-arginine analog, which is markedly deleterious to these larvae. Homoarginine is incorporated into M. sexta lysozyme, and the antibacterial proteins of the fly, Phormia terranovae with impunity. In contrast, the comparable canavanine-containing enzymes are inhibited severely. Experimental evidence is presented that the innocuous nature of homoarginine results from the elevated pKa value of its guanidino group which arguably exceeds even that of arginine. As a result, homoarginine does not disrupt essential residue interactions. In contrast canavanine, which is much less basic than arginine, does adversely affect R group interactions forming the requisite three-dimensional conformation of the protein.

Animals↗
PubMed1994

Labeling with 15N as compared with homoarginine suggests a lower prececal digestibility of casein in pigs.

Calculations of prececal protein digestibility based on the stable isotope 15N and the chemical label homoarginine were compared, using casein doubly-labeled with both markers. After food was withheld overnight 24 miniature pigs were given a meal containing 15 g/100 g casein, including 4 g/100 g doubly-labeled protein, and chromic oxide as an indigestible marker. The intestine of eight animals each was removed 3, 6 or 12 h later, divided into 3 sections of equal length, and chyme was collected. Kjeldahl-N, 15N and homoarginine were determined in diet and chyme. Digestibility of casein in the distal third of the small intestine was 93.5 +/- 0.5% and 97.6 +/- 0.3% (P < 0.05) according to 15N and homoarginine label, respectively. Potential causes for this systematic difference were assessed. The data suggest that incorporation of 15N into endogenous proteins and re-entry into the intestinal lumen via secreta and desquamations is the major cause for the 4.2 +/- 0.4% lower digestibility based on the 15N as compared with the homoarginine labeling technique. A preferential occurrence of homoarginine in more easily digestible sections of the protein, faster release during the digestive process and absorption of homoarginine, or incorporation of 15N into proteins of intestinal bacteria are less likely to cause this difference.

Animals↗
PubMedDate not supplied

The effect of homoarginine on the EEG of rats.

The effect of homoarginine on electroencephalographic activity in the rat was investigated. Electroencephalograms with epidural electrodes revealed spike discharges after topical application of homoarginine on pia mater. Spike discharges disappeared when homoarginine was removed by washing after spike discharges had begun. The critical concentration to induce spike discharges was in the area of 100 mM. By intracisternal injection of homoarginine, negative spike discharges and positive spike discharges were observed only with unipolar recordings. Our results suggested that the epileptogenic character of homoarginine could be involved in the pathophysiology of the so-called "rum fit" associated with the alcohol withdrawal syndrome.

Action Potentials↗
PubMed1967

Inhibition of Escherichia coli B by homoarginine.

Homoarginine inhibits the growth of Escherichia coli B, but not of E. coli K-12. These two strains also differ in regard to repressibility of the arginine-forming enzymes. In K-12, arginine acts as a repressor whereas in B it does not. The latter difference is determined by different alleles of a regulator gene, arg R. In K-12 x B crosses, it was shown that the genetic determinant for homoarginine sensitivity is closely linked to or identical with arg R. Homoarginine-resistant mutants of B were isolated. The biochemical mechanism of homoarginine inhibition is not known. However, whether or not a strain is sensitive to homoarginine seems to depend on the intracellular level of arginine. In B this level is relatively low and inflexible as a result of the action of a repressor whose formation is determined by the B-specific allele of arg R.

Arginine↗
PubMed1997

Evaluation of homoarginine as a marker for the determination of endogenous amino acid concentrations in poultry excreta.

1. Endogenous amino acid losses in ileal digesta and excreta of adults cockerels fed on diets containing guanidinated forms of casein, soyabean meal and cottonseed meal were determined using homoarginine as a marker. 2. The ileal endogenous amino acid losses were markedly higher (P < 0.001) in birds given the cottonseed meal diet compared to those given the other two diets. The ileal endogenous protein was rich in aspartic acid, serine and glutamic acid. 3. Negative values were obtained for endogenous amino acid output in excreta. These aberrant values were caused by high concentrations of homoarginine in the excreta. A subsequent study with broiler chickens showed that the homoarginine in excreta was of urinary origin. 4. These results indicate that the homoarginine technique is not suitable for determining endogenous amino acid losses in excreta, but applicable when determinations are made in the terminal ileum.

Amino Acids↗
PubMed1997

Homoarginine influences voluntary feed intake, tissue basic amino acid concentrations and arginase activity in chickens.

Two experiments were conducted to investigate the factors responsible for the adverse effects of guanidinated proteins on feed intake in chickens. In Experiment 1, male broiler chicks were fed one of five purified diets containing casein or guanidinated casein (G-casein) as the sole source of protein (230 g crude protein/kg diet) from d 6 to 13 post-hatching. A casein-based diet containing 17.2 g lysine/kg, served as the control. In the experimental diets, casein was substituted by G-casein and lysine was added at 0, 5.6, 11.4 and 17.0 g/kg diet, respectively. Feed intake and weight gains of chicks fed the G-casein diet without added lysine were markedly depressed (P < 0.05), but this depression was largely overcome by additional lysine. The intake and gains of chicks fed the G-casein diet plus 17.0 g lysine/kg were lower (P < 0.05) than those fed the G-casein diet plus 11.4 g lysine/kg and this was associated with a higher plasma lysine:arginine ratio. Tissue analysis showed that homoarginine is distributed throughout body tissues following absorption. Brain lysine concentrations were lower (P < 0.05) in chicks fed diets containing G-casein without added lysine, but increased (P < 0.05) with supplemental lysine. In Experiment 2, the effect of homoarginine per se on feed intake was investigated in two short-term intake studies using 5-wk-old broiler chickens. Significant (P < 0.05) depressions in feed intake were observed within the first hour after oral administration of 400 mg homoarginine-HCl. The results suggest that both lysine deficiency and homoarginine per se were responsible for the adverse effects of guanidinated proteins on feed intake in chickens.

Amino Acids, Essential↗
PubMed2002

Evaluation of the homoarginine technique for measuring true ileal amino acid digestibilities in pigs fed a barley-canola meal-based diet.

The homoarginine technique has been suggested as a means to determine true ileal amino acid digestibilities in nonruminant animals fed protein-containing diets. Conditions for guanidinating lysine to homoarginine in barley and canola meal and the effect of this process on nutrient composition and ileal digestibilities in the resulting material were investigated. Conditions tested were methylisourea concentration (0.4, 0.5, or 0.6 M) and reaction time (4 or 6 d) at pH 10.5. Using 0.4 methylisourea M solution for 4 or 6 d gave guanidination rates of 72.5 and 78.5% for barley and 72.3 and 75.2% for canola meal, respectively. Using 0.5 M gave 88.0 and 84.6% guanidination rates in barley and canola meal, respectively, after a 6-d reaction time. Under these conditions, guanidination did not change the nutrient composition of barley (P > 0.10), whereas it increased CP (38.4 vs 49.0%), crude fiber (10.2 vs 16.0%), acid detergent fiber (30.0 vs 43.4%) and neutral detergent fiber (29.8 vs 49.4%) levels in canola meal (P < 0.05). Four 33.6-kg barrows fitted with a simple T-cannula at the terminal ileum were fed a 16% CP unguanidinated barley and canola meal-based diet for four consecutive 14-d periods. Ileal digesta were collected continuously for 24 h on d 12 and 14 to determine apparent nutrient digestibilities. On the morning of d 14, pigs were fed a diet in which half of the barley and canola meal was replaced with guanidinated material for determining true ileal amino acid digestibilities. Digesta samples were pooled by pig and by 24-h period to give 16 observations per diet. Apparent ileal digestibilities of DM, CP, and AA in the unguanidinated and guanidinated barley-canola meal diet were similar (P > 0.10) despite the changes observed in canola meal. Apparent ileal lysine digestibility was 73.9 and 74.5% in the unguanidinated and guanidinated diet, respectively. The true ileal lysine digestibility was 88.1%. The present results show that guanidination does not interfere with digestion and further support the use of the homoarginine method for determining true ileal amino acid digestibilities in pigs fed practical diets. A methylisourea solution of 0.5 M and a 6-d reaction time are recommended for converting lysine to homoarginine in barley and canola meal.

Amino Acids↗
PubMed1979

Kinetics of hydrolysis of phenylthiazolones of arginine, homoarginine, norarginine, and canaavanine by trypsin.

Phenylthiazolones (PTAs) of arginine and its homologs and analogs, homoarginine, norarginine (alpha-amino-gamma-guanidinobutyric acid), canavanine, and gamma-hydroxyarginine, were prepared. A steady-state kinetic analysis of the trypsin [EC 3.4.21.4]-catalyzed hydrolysis reactions was carried out and the kinetic parameters for these internal thioesters were compared with those for normal linear ester substrates. PTA-gamma-hydroxyarginine was so labile that hydrolysis by the enzyme could not be followed. PTA-arginine has a specificity constant (Kcat/Km) comparable to that for the Nalpha-unblocked arginine ester substrate, though the value is about 0.1% of that for a specific ester substrate, Nalpha-tosylarginine methyl ester. PTA derivatives of canavanine and homoarginine were hydrolyzed with Kcat/Km walues of the same order of magnitude as that for PTA-arginine. However, PTA-noraginine was much less susceptible to tryptic hydrolysis that PTA-homoarginine, while the linear esters of norarginine are known to be more susceptible than those of homoarginine.

Arginine↗
PubMed1979

[12-Homoarginine]glucagon: synthesis and observations on conformation, biological activity, and copper-mediated peptide cleavage.

Specific modification of the single lysine residue (Lys-12) in glucagon with O-methylisourea has been effected by blocking the reactivity of the amino terminal histidine with copper, providing a method for obtaining [12-homoarginine]glucagon. It was found that as a side reaction, under the conditions of the modification reaction, Cu(II) catalyzed cleavage of the polypeptide chain between Asp-9 and Tyr-10, and between Lys-12 and Tyr-13. This observation may be of value for development of a sequence-specific peptide cleavage procedure. The dilute solution conformations of glucagon and [12-homoarginine]-glucagon were compared by circular dichroism, fluorescence, phosphorescence, energy transfer, and optical detection of magnetic resonance. The results indicate that conversion of Lys-12 to homoarginine does not alter the helix content the side chain conformation in the vicinity of the tyrosine and tryptophan residues, or the relative distances and orientations between these residues. However, the modification reduces the hormone potency towards activation of lipolysis in isolated rat epididymal fat cells by a factor of seven. We attribute the loss of potency to an interference with a specific interaction between the lysine residue and the fat cell hormone receptor, and not to a change in the solution conformation of the hormone.

Adipose Tissue↗