Ding Chang

Inhibition of gastric acid secretion in dogs by neurotensin.

Abstract Neurotensin is a tridacapeptide which has been isolated from bovine hypothalamus. The action of synthetic neurotensin was studied on gastric acid secretion in dogs provided with gastric pouches. Intravenously infused neurotensin, 50 ng × kg −1 × min −1 , was found to produce a considerable inhibition of pentagastrin stimulated gastric acid secretion. On the other hand, there was no sign of inhibition of histamine induced gastric acid secretion. The experiments show that neurotensin, isolated from the central nervous system is a potent gastric secretory inhibitor and that it has a selective action in inhibiting gastric acid responses to pentagastrin but not to histamine.

Effect of synthetic substance P on monoaminergic mechanisms in brain

Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N′-(DL-seryl)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamme, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia.

Partial reactivation of impaired immune competence in aged mice by synthetic thymus factors.

Abstract Our results clearly show the profound impairment of the humoral, hemolytic, primary, immune response in aged mice (22 months) as compared with this response in young (10 weeks) mice. A partial but significant reactivation of the age-determined impairment of the immunological responsiveness results from subcutaneous administration of two newly synthesized thymus factors and one analog. These synthetic thymus peptide factors correspond to factors previously isolated and identified in thymus glands or blood.

Mass spectra of underivatized peptide amides related to substance P.

Abstract Mass spectra of underivatized hexa- and heptapeptide amides related to Substance P have been obtained with a conventional electron ionization mass spectrometer using sample vaporization from a tungsten wire by the technique of rapid heating, proton transfer ionization using ammonia, and photoplate recording of spectra. These spectra exhibit little evidence of sample pyrolysis and are readily interpreted to yield amino acid sequences.

Substance P found to lower body temperature and aggression

Abstract Synthetic substance P (SP) was bioassayed in mice by a procedure comprising eleven subtests. Two replications of a dose-response study were conducted at the time of the peak effect of the intravenous injection of SP. Single doses of 31 and 63 ng/kg significantly decreased body temperature. SP, [D-Arg1]-SP, and [des-NH2-Arg1]-SP comparably lowered blood pressure, but [D-Arg1]-SP and [des-NH2-Arg1]-SP were 1 20 to 1 10 as active as SP in lowering body temperature. The activities that lower body temperature and blood pressure may be different. The thyrotropin and luteinizing hormone releasing hormones (TRH and LH-RH) did not lower body temperature. SP also decreased the aggressive response (ED50, 89 ng/kg).

Differentiation of factor C-LHIH and the synthetic contraceptive polypeptide, H-Thr-Pro-Arg-Lys-OH

Summary The contraceptive polypeptide designated by Kent and shown by him to be H-Thr-Pro-Arg-Lys-OH has been synthesized by a solid-phase procedure, and the tetrapeptide was purified and characterized. Factor C-LHIH, partially purified from porcine hypothalami, which inhibits the luteinizing hormone from basal release and from the synthetic luteinizing hormone releasing hormone (LHRH), and the synthetic H-Thr-Pro-Agr-Lys-OH are different by cation exchange and by other high pressure liquid chromatographic techniques. At high dosage, H-Thr-Pro-Arg-Lys-OH released FSH and to a lesser extent LH, but the tetrapeptide showed no antagonist activity against synthetic LHRH, even at very high levels.

Synthesis of [Gln4]-neurotensin using a new solid support, the 4-(hydroxymethyl)phenylacetamidomethyl-resin

Abstract For biomedical studies, [Gln4]-neurotensin, which appears to be the naturally occurring form of neurotensin, was synthesized using a recently designed new resin for the Merrifield solid-phase synthesis of peptides, 4-(hydroxymethyl)phenylacetamidomethyl resin (PAM-resin). This synthesis was compared to the synthesis of [Gln4]-neurotensin by the use of oxymethyl-copoly-(styrene-divinylbenzene) as the solid support. The PAM-resin was superior, since the yield of [Gln4]-neurotensin was doubled and fewer purification steps were necessary.

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.