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K Nikolics

Publications and source records attributed to K Nikolics.

At least 73 records · Page 4Linked to original sources
PubMed1982

The site of histone H2b phosphorylated by a cyclic nucleotide independent histone kinase.

A cyclic nucleotide independent histone kinase was demonstrated in bovine thymus extract. This enzyme was very similar to that found previously in the cytoplasm and nucleus of human tonsillar lymphocytes (Faragó et al., 1973, Biochim. Biophys. Acta 297, 517 and 1974, ibid 370, 459). High-performance liquid chromatography of the tryptic phosphopeptides of calf thymus histones H1 and H2b phosphorylated by the histone kinase or by the catalytic subunit of cylic AMP dependent protein kinase showed that the intrinsic substrate specificity of these enzymes differed significantly. Under our experimental conditions the histone kinase phosphorylated preferentially the Ser-32 residue, and it did not phosphorylate the Ser-36 residue of histone H2b, while Ser-36 was phosphorylated preferentially by the cyclic AMP dependent protein kinase. A peptide containing the amino acid sequence of histone H2b from Gly-26 to Lys-34 (Gly-Lys-Lys-Arg-Lys-Arg-Ser-Arg-Lys-Ala) was synthesized. This peptide was a competitive inhibitor of histone H1 phosphorylation by the histone kinase and it was also a substrate for this enzyme.

Amino Acid Sequence↗
PubMed1982

Protection of methionine in peptides during iodination by sulfonium salt formation.

A method for the prevention of methionine oxidation during iodination of tyrosine containing peptides is reported. The methionine containing peptide is converted into the corresponding S-tert.-butylsulfonium derivative, which is iodinated using iodine monochloride. After removal of the S-tert.-butyl group and purification, sulfoxide-free 3,5 diiodotyrosine (Dit) peptides were obtained. Dit8-substance P, Dit8-physalaemin 6-11 and Dit1, Met5-enkephalin were synthesized by this route. Tritium labeling of Dit1, Met5-enkephalin yielded 3H-enkephalin with a specific radioactivity of 38 Ci/mmol.

Enkephalin, Methionine↗
PubMed1981

Inhibition of LH-release by synthetic analogues of LH-RH in rat pituitary cell culture.

Conditions for testing the inhibitory activity of synthetic analogues of LH-RH in monolayer cultures of rat pituitary cells were optimized. Nine synthetic derivatives of LH-RH were tested to evaluate their inhibitory dose50(ID50) values. The peptide antagonists tested included linear, branched-chain, dimeric and tetrameric derivatives of LH-RH, Ac-D-Phe1, D-Cpa2, D-Trp3,6-LH-RH (analogue V) was found to be the most effective competitive inhibitor of the series with an ID50 value of 6 x 10(-9)M in the presence of 10(-9) M LH-RH. The kinetics of the LH-RH-blocking action of two inhibitors were also studied. Both the linear (analogue I) and the dimeric (analogue VI) peptide showed immediate inhibition of HL-release. Prolonged inhibitory activity of the same two peptides was observed when cells were incubated with LH-Rh subsequent to preincubation with the inhibitors.

Animals↗
PubMed1981

Tritium labeling of gonadotropin releasing hormone in its proline and histidine residues.

3,4-dehydroproline9-GnRH prepared by solid phase peptide synthesis was tritiated catalytically under various conditions yielding 3H-GnRH with specific radioactivities in the range from 35-60 Ci/mmol and full LH releasing activity in vitro. Using palladium/alumina catalyst, the tritiation of the double bond occurs within ten minutes. Investigation of the tritium distribution between the amino acid residues showed a remarkably high incorporation of tritium into the histidine residue (11 to 37%). On the basis of this observation, the tritium labeling of GnRH and angiotensin I by direct catalytic hydrogen-tritium exchange was found to be useful for the labeling of these peptides at remarkably high specific radioactivity.

Aluminum Oxide↗
PubMed1980

Effect of a synthetic LH-RH agonist on the endocrine function of the testis, adrenocortex and thyroid gland in cocks.

Testosterone, progesterone, thyroxine and triiodothyronine levels in peripheral plasma of cocks and capons were determined by RIA, corticosteroid contents by CPB method 10, 20 and 30 min as well as 1, 2 and 4 hr following a single intravenous injection of 0.5 micrograms/kg D-Lys6-LH-RH ethylamide. Testosterone level increased after 30 min, reached a peak after 1 hr, and returned after 4 hr to the control level in cocks. Plasma concentrations of progesterone and triiodothyronine did not change in response to the treatment. Thyroxine plasma level increased in cocks simultaneously with the decrease of testosterone contents between 1 and 2 hr. In capons, the increase of thyroxine did not occur, thus the promoting factor was probably not LH-RH but rather the decrease of the high testosterone level. Corticosterone level increased between the 2nd and the 4th hr in cocks and between the 1st and 4th hr in capons. This increase might have been due to the increase in thyroxine level (cocks) and the immediate stimulatory effect of the LH-RH analogue of not the C-RH type (cocks, capons).

Adrenal Cortex↗
PubMed1978

Disapearance and excretion of labeled alpha-MSH in man.

Despite the considerable evidence for the CNS actions of alpha-melanocyte-stimulating hormone (alpha-MSH) in man, little attention has been given to its half-time disappearance from plasma and urinary excretion in normal individuals. In the first experiment, a healthy man was given 15 muCi of tritiated (3H)-alpha-MSH as a rapid IV injection. A plot of the disappearance time in plasma was characteristic of a multiexponential curve, the linear components of which were resolved by the subtraction method and half-time disappearance calculated directly from the slope of the regression line. The half-time disappearance was 1 min for the first component and 25 min for the second component. After the IV adminisration of 50 muCi of 125I-alpha-MSH in the second experiment, the two components showed halftime disappearances of 1 min and 4.8 min respectively. These times were not changed by precipitation of the plasma with 10% trichloroacetic acid. Thirty-eight percent and 42% of the label appeared in the urine 4 hr after the injection of either 3H-alpha-MSH or 125I-alpha-MSH. The results suggest that the persistence of high levels of alpha-MSH in the blood after injection in man may be too short to fully explain the CNS effects of alpha-MSH.

Humans↗
PubMed1977

Suppression of gonadotrophin release in many by an inhibitory analogue of L.H.-releasing hormone.

The ability of an inhibitory analogue of L.H.-releasing hormone (L.H.R.H.) to suppress the release of luteinising hormone (L.H.) and follicle-stimulating hormone (F.S.H.) after administration of a small does of L.H.R.H. was tested in four men. A single intramuscular injection of 90 mg (D-Phe-2,D-Trp-3,D-Phe-6)-L.H.R.H. diminished the gonadotrophin response to 25 micrometer of L.H.R.H. given 1, 4, 8, and 24 hours afterwards. Basal levels of L.H. and F.S.H. were not lowered. The results demonstrate that an inhibitory analogue of L.H.R.H. is active in man and suggest the possibility that inhibitors of L.H.R.H. might eventually form the basis of a new method of birth control.

Follicle Stimulating Hormone↗
PubMed1977

Synthesis and biological activity of position 1 analogs of LH-RH.

(Formyl-sarcosine)1-LH-RH (I), (acetyl-sarcosine)1-LH-RH (II), (2-pyrrolidone-4-carboxylic acid)1-LH-RH (III), (N-methyl-2-pyrrolidone-4-carboxylic acid)1-LH-RH (IV, hydroxyproline1-LH-RH (V) and (cylcopentane-carboxylic acid)1-LH-RH (VI) were synthesized by solid phase methods on a benzhydrylamine resin support. Peptides I-IV were assayed for LH- and FSH-releasing activity over a 4-h period after subcutaneous infection into immature male rats in order to detect any prolongation ofactivity. The peptides were found to have the following integrated LH-releasing activities compared with LH-RH: I, 64%; II, 72%; III, 19%; IV, 58%. None of the peptides were found to be longer acting than LH-RH. Peptides V and VI were far less active, 0.001% and 1.4%, respectively.

Amino Acids↗
PubMed1976

Peptides readily penetrate the blood-brain barrier: uptake of peptides by synaptosomes is passive.

The intracarotid artery quick injection technique of Oldendorf was utilized to determine the Brain Uptake Index (BUI) of radio-labeled peptides in comparison with 3H2O or 14C-antipyrine as counterlabels. The normalized BUI values for 3H-MIF-I, 3H-alpha-MSH and 14C-AVP were 13.7, 9.6 and 13.0 respectively at 15 sec after injection consistent with their having readily penetrated the blood-brain barrier. The BUI values were similar, though somewhat increased, at 10 min postinjection consistent with their ready exit across the blood-brain barrier. At 15 sec after injection 0.5+/-0.1%/g brain of the originally injected peptide label was recovered; and 0.1+/-0.2%/g brain was recovered after 10 min. The label was distributed uniformly in the major brain regions at both times. However, the percentage of the originally injected label/g of pineal and pituitary gland tissue was 10-20 X increased as compared with the major brain regions as would be expected by their location outside the blood-brain barrier. The in vitro uptake of the radio-labeled peptides by synaptosomes prepared from the whole brain and the major brain regions was passive; it was not temperature dependent, nor was it Na+ dependent. However, the binding of the three peptides by the synaptosomes varied considerably: AVP greater than MSH greater MIF: 50 greater than 5 greater 1. The penetratin of the blood-brain barrier by the three peptides is consistent with their having CNS effects.

Animals↗
PubMedDate not supplied

Proteolytic degradation of gonadotropin-releasing hormone (GnRH) by rat ovarian fractions in vitro.

GnRH in physiological concentrations is highly degradable by both soluble and particulate fractions of rat ovarian homogenate in vitro. The two proteolytic enzyme activities differ strongly by the soluble activity showing a dithiothreitol optimum, high inhibition by diisopropyl fluorophospate (ki = 0.7 microM), and a relatively high affinity (Km = 1.1 microM) as opposed to the particulate fraction (Ki = 3.5 mM and Km = 150 microM, respectively). The results of this study show that the rat ovary is differently endowed with GnRH-degrading activity at different sites. The involvement of these in terminating the biological activity of the hormone on the ovary may possibly depend on its exact pathway in this GnRH-target organ.

Animals↗
PubMedDate not supplied

In vitro LH release and cAMP accumulation induced by synthetic GnRH derivatives.

The LH-releasing activity of GnRH and nine synthetic GnRH derivatives was tested in pituitary monolayer cell culture prepared from female rats. D-amino acid-substituted analogs were found to be 12 to 18-fold as active as GnRH, while D-amino acid GnRH-[1-9]-ethylamide analogs showed 15 to 38-fold activity as compared to GnRH. Dehydroproline-GnRH was equipotent with the parent compound. Asp(A)6-GnRH-EA was less active than GnRH and it was a partial agonist only. All peptides stimulated intracellular cAMP content of the cultured cells at 1 hr and 4 hr of incubation. A nearly uniform 1.8 to 2-fold increase above basal cAMP could be observed with all peptides tested at their maximally active concentrations. However, no correlation could be established between the relative LH-releasing activities and cAMP-elevating potencies of the peptides. The findings suggest that cAMP may not be involved in overall LH-release by GnRH but leave the possibility open that cAMP could be involved in certain steps of mobilizing compartmentalized LH pools of pituitary gonadotrophs.

Animals↗