Cyclic Nucleotides And The Regulation Of Cell Growth

Cell Fractionation by Centrifugation Methods.- - Introduction.- - Homogenization.- - Fractionation methods.- - Analysis of the fractions and interpretation of the results.- - Conclusion.- - References.- Binding of Ligands to Receptors: Theory.- - Introduction.- - Experimental approach to the hormone-receptor interaction.- - Molecular models of receptors.- - Graphical representations of saturation experiments.- - Methodologic errors and graphical representations.- - Conclusion.- - References.- On the Modes of Regulation of Intracellular Cyclic AMP: Desensitization of Adenylyl Cyclases to Hormon.

The brilliant research of Dr. Earl Sutherland and his colleagues has had a broad impact on many areas of biology. Among the fields in fluenced rather late by the insights arising from this work were im munology and oncology. Although research relating cyclic AMP metabol ism to the development and manifestations of the immune response and the control of mammalian cell growth is relatively recent, the growth of knowledge in these areas has been rapid and there is already a considera ble amount of empirical information. This conference provided an oppor tunity to collate and begin to interpret that information. A deliberate at tempt was made to bring together investigators nominally involved in im munology, biochemistry, pharmacology, or cellular biology for in many instances parallel observations are being obtained in these fields. For ex ample, the immunologist studying the transformation of lymphocytes by antigens or mitogens is carrying out experiments that are very close to those of the biologist studying the growth of cells in culture; in both cases, the phenomena they observe are modulated by changes in the in tracellular level of cyclic nucleotides. Many other examples of closely analogous experiments in different fields could be cited, but perhaps the point is clear.

The aim of this work was to elucidate the effect of cyclic nucleotide signaling on the growth of vascular smooth muscle cells (VSMCs). In particular, the role of cGKI in VSMC growth was analysed in primary and subcultured VSMCs derived from wild-type and cGKI-deficient mice. In primary VSMCs, activation of cGMP/cGKI signaling led to a strong increase in growth. In contrast, in repeatedly passaged VSMCs derived from mouse, rat and human, cGMP/cGKI had either no effect on growth or had a weak growth suppressing effect. Thus, cGKI signaling differs in primary vs. subcultured VSMCs. The further analysis of proliferation, apoptosis, cytoskeletal dynamics, and various signaling pathways indicated that an increase in integrin-mediated cell adhesion is the major mechanism for cGKI-mediated growth in primary VSMCs. Thereby, cGMP/cGKI signaling in primary VSMCs might inhibit anoïkis, the programmed cell death induced by the loss of cell/matrix interactions.

Growth, Nutrition, and Metabolism of Cells in Culture, Volume 3, focuses on a number of specific, timely areas of research that make use of cell and tissue culture. The major theme of this volume is growth and its regulation in animal cells. The book includes studies on the role of growth factors in cell culture systems; the effects of cyclic nucleotides in cell proliferation in culture; metabolic regulation during the cell cycle; and the role of the cell surface in growth and metabolic regulation. There are also separate chapters on aspects of abnormal cell growth and metabolism; DNA repair; genetic analysis using cell fusion techniques; the growth of vascular cells in culture for atherosclerosis research; the culture of haploid vertebrate cells for genetic analysis of cell function; data on haploid cell culture; and the value of using cell cultures to test for the possible toxicity of various pharmacologic agents.