ABSTRACT
A synthetic analogue of a pentapeptide associated with mature granulocytes has been described earlier and shown to suppress myelopoietic colony formation in vitro in concentrations from 10(-13) to 10(-6) M. By oxidation of the peptide, a dimer will rapidly occur by formation of disulfide bridges between cysteine residues. We here demonstrate that this dimer has the opposite effects of the monomer. For both mouse and human granulocyte-macrophage colony-forming units (CFU-GM), a dose-dependent enhancement of colony formation was observed in the dose range 10(-16) to 10(-5) M, where a saturation level was reached above 10(-8) M. At low doses of colony-stimulating activity (CSA) and in the linear stimulating phase, an up to ten times increase of colony formation was seen, whereas at higher doses the effect was less pronounced. Also at the plateau level of CSA stimulation an increased colony yield was seen. All types of colonies were stimulated. The dimer itself had no colony-stimulating factor activity and was not toxic to bone marrow cells in suspension cultures up to 24 h. Upon reduction of the dimer by use of sulfhydryl compounds, inhibitory effects on CFU-GM were restored. The peptide had no effect on the phagocytic process in human granulocytes, including attachment and internalization of bacteria or Zymosan particles. The monomerdimer equilibrium of hemoregulatory peptide may constitute a new mechanism for proliferative regulation of myelopoietic cells.
Subject(s)
Bone Marrow/physiology , Hematopoiesis/drug effects , Oligopeptides/pharmacology , Agar , Animals , Bone Marrow/drug effects , Bone Marrow Cells , Colony-Forming Units Assay , Colony-Stimulating Factors/isolation & purification , Colony-Stimulating Factors/pharmacology , Colony-Stimulating Factors/toxicity , Disulfides , Endotoxins/analysis , Female , Humans , Mice , Mice, Inbred C3H , Oligopeptides/isolation & purification , Oligopeptides/toxicity , Phagocytosis/drug effects , Pyrrolidonecarboxylic Acid/analogs & derivatives , Structure-Activity RelationshipABSTRACT
The tetrapeptide pyroGlu-Glu-Asp-GlyOH and its gamma-amide have been isolated from the urines of lipodystrophic patients with insulin-resistant diabetes. Both peptides induce insulin release only at high blood glucose levels.
Subject(s)
Diabetes Mellitus, Lipoatrophic/urine , Insulin/metabolism , Oligopeptides/urine , Animals , Blood Glucose/analysis , Humans , Insulin Secretion , Male , Oligopeptides/isolation & purification , Oligopeptides/physiology , Pyrrolidonecarboxylic Acid/analogs & derivatives , Rats , Rats, Inbred StrainsABSTRACT
Peptidic neurones may be considered as multisignal intergrators and transducers. When formation or release of peptide outstrips genetically determined breakdown capacity, overflow of peptides to the body fluids and urine may be expected. In this paper, pathological urinary chromatographic patterns of peptides are shown for genetic, functional and mixed disorders. Part symptoms of the disorders may be induced with the biologically isolated and purified peptides as well as with chemically synthesized peptides.
