Johann J. Leban

Neurotensin and its amide analogue [Gln4]-neurotensin: effects on brain monoamine turnover.

SummaryIntracerebroventricularly administered neurotensin and [Gln4]-neurotensin (50–200 μg) increased the formation of Dopa in different brain regions of rats after inhibition of the aromatic l-amino acid decarboxylase. For both neuropeptides these increases were dose dependent (20–150%). In the corpus striatum [Gln4]-neurotensin was twice as active as neurotensin and it tended to be more active also in other brain regions. The brain tyrosine concentrations were also increased. [Gln4]-neurotensin (100–200 μg) following inhibition of the aromatic l-amino acid decarboxylase, increased the accumulation of 5-hydroxytryptophan in all brain regions by 30–60%. In contrast, neurotensin was completely inactive. In both cases the brain tryptophan concentrations were increased. Both neurotensin and [Gln4]-neurotensin also accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. These results show an increased brain monoamine turnover induced by both neuropeptides.

On the existence and separation of the follicle stimulating hormone releasing hormone from the luteinizing hormone releasing hormone

Porcine hypothalamic fragments were extracted by 2M AcOH at 4°C, and the extractives were subsequently processed in the presence of one protease inhibitor and one anti-oxidant. Gel filtration was performed on Bio-Gel P-2, and supplementary [3H]-LHRH and [14C]- <GluOH were used. The fractions of elution were assayed for both LH- and FSH-releasing activities and for radioactivities. An entity which unambiguously released FSH was separated from [3H]-LHRH, and was differentiated from [14C]- <GluOH and N-Ac-AspOH. This entity may be presumed to be FSHRH, and if so, it may have a molecular weight larger than that of the decapeptide, LHRH.

Isolation of glutathione from bovine thymus and its significance to research relevant to immune systems

A peptide was isolated from bovine thymus when a cAMP assay guided fractionation; it was glutathione. Pure glutathione (isolated and purchased) at 1, 10, 20, 40 and 100 μg/ml was active, P<0.05–0.01, in the cAMP assay. Glutathione was not active in the mixed lymphocyte culture assay, but was active in assays using T-rosettes. Glutathione may now be separated to avoid its biological interference in assays guiding fractionation to a thymic hormone(s). It is credible that glutathione was in fractions studied biologically and clinically by others. Knowing that glutathione may function in the transport of amino acids across membranes, and that L-alanine is essential for human lymphocytes to respond to mitogenic and allogenic stimulation, it seems possible that glutathione might be functional in the complex immune systems.

A synthetic peptide capable of eliciting antibodies that neutralize human chorionic gonadotropin**This work was undertaken as part of the contraceptive development research program sponsored and coordinated by the International Committee for Contraception Research of the Population Council, Inc., New York, New York. The financial support provided by the International Development Research Center of Canada, The Ford Foundation, The Rockefeller Foundation, and the George J. Hecht Fund is gratefully acknowledged.

Antisera generated to the human chorionic gonadotropin beta-subunit (hCGbeta) have been shown not only to neutralize the biologic activity of hCG but also to cross-react with human luteinizing hormone (hLH). In an attempt to reduce such cross-reactivity, a peptide fragment analogous to the amino acid sequence of the carboxylterminal 45 residues (101-145) of the hCGbeta-subunit with alpha-aminobutyric acid substituting for cysteine at position 110 was synthesized and tested for ability to produce antibodies interacting with hCG. Antisera were generated in rabbits to a conjugate of this peptide with tetanus toxoid emulsified with Freunds complete adjuvant. Antibody titers and specificity were assessed by the double-antibody technique. The results show that the antisera to the synthetic hCGbeta fragment bound 125I-labeled hCG and did not cross-react with hLH in the radioimmunoassay system. Most importantly, the antisera effectively neutralized the biologic activity of hCG as determined by the rat uterine weight assay.