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Biomedical subjects

C Poulos

Publications and source records attributed to C Poulos.

28 records · Page 2Linked to original sources
PubMed1989

Regulation of macrophage apolipoprotein E gene expression by cholesterol.

The relationship between macrophage cholesterol content and apolipoprotein E (apoE) gene expression was investigated in cultured mouse peritoneal macrophages. Acetylated low density lipoprotein (ALDL) at 25 micrograms/ml led to increased macrophage messenger RNA abundance as detected by Northern blot hybridization. Incubation in a range of ALDL concentrations (0-100 microgram/ml) led to graded increases in macrophage free and esterified cholesterol, and apoE mRNA detected by slot blot hybridization. After a 2-h pulse of ALDL, with or without acyl-CoA:cholesterol acyltransferase inhibition, increased apoE mRNA was not detected until after 6 h. Removal of cholesterol from upregulated macrophages, using human high density lipoprotein, resulted in a return of apoE mRNA levels toward baseline. Nuclear run-off transcription assays demonstrated increased apoE gene transcription in macrophages incubated with ALDL. It is concluded that: a) previously reported changes in macrophage apoE content and secretion after cholesterol enrichment or depletion can be attributed to changes in apoE mRNA levels; and b) cholesterol-induced changes in apoE mRNA are associated with increased apoE gene transcription.

Animals↗
PubMed1987

Structure-activity studies on the C-terminal hexapeptide of substance P with modifications at the glutaminyl and methioninyl residues.

Analogues of [Orn6]-SP6-11 have been synthesized in which the SCH3 group of the Met11 side chain is replaced by other functional groups, such as (CH2)2NH2, COOH, CONH2, and COOR, which have basic, acid, or neutral character and which may act as either H-bonding donors or H-bonding acceptors. These analogues were tested in guinea pig ileum and rat colon muscularis mucosae, in vitro. Substitution of Lys, Gln, or Glu at position 11 caused a marked reduction in biological activity in both tissues. In contrast, the glutamate benzyl ester analogue had only slightly reduced activity in the guinea pig ileum and an increased (4.7 times) activity in the rat colon. It is concluded that charged groups in the side chain at position 11 of SP6-11 reduce the biological activity of SP hexapeptide.

Amino Acid Sequence↗
PubMed1986

Synthesis and biological activity of substance P C-terminal hexapeptide analogues: structure-activity studies.

A series of analogues of the C-terminal hexapeptide of substance P, modified at the glutaminyl residue, was synthesized and their relative activities as spasmogens were determined in the guinea pig ileum and rat colon muscularis mucosae preparations in vitro. In general, when compared to SP6-11, the loss of the carboxamide group has little effect on activity in the colon and reduces activity on the ileum. The exception to this is the Orn6 analogue which retains activity on both preparations and is proposed as a useful tool for structure-activity studies. It is concluded that the hydrogen-bonding potential of the position 6 substituent may be an important determinant of biological activity.

Animals↗
PubMed1985

Conformationally restricted C-terminal peptides of substance P. Synthesis, mass spectral analysis and pharmacological properties.

Four cyclic analogues of the C-terminal hepta- or hexapeptide of substance P were prepared by the solution method. The cyclizations were obtained by substituting with cysteine the residues normally present in positions 5 or 6 or 11 of substance P and by subsequent disulfide bond formation. The final products were identified by ordinary analytical procedures and advanced mass spectroscopy. The biological activities were determined on three bioassays: the guinea pig ileum, the guinea pig trachea and the rabbit mesenteric vein. Results obtained with these assays indicate that all peptides with a disulfide bridgehead in position 11 are inactive and that a cycle between positions 5 and 6 already strongly reduces the biological activity. The acyclic precursors containing thiol protection groups display weak biological activities. These results further underline the importance of the side chain in position 11 of substance P and suggest that optimal biological activities may require a linear peptide sequence.

Animals↗
PubMed1982

Structure-activity studies on the C-terminal amide of substance P.

Twelve C-terminal heptapeptide analogues of substance P have been synthesized by solid phase and by the classical solution method. The modifications concerned all the C-terminal primary amide of SP and should therefore help to understand the biological significance of this carboxamide, as evaluated by in vivo and in vitro bioassays. From the results it can be seen that not the slightest change of the two amide protons is tolerated without an important loss of activity: replacement of one or two amide protons with alkyl groups, extension of the amide to the hydrazide and its alkyl analogues, and exchange of the amide with an ester or a carboxylic acid all reduce the relative activity/affinity at least by 2-fold. It is not clear for what reason all these modifications produce such a drastic activity reduction.

Animals↗