Date of Award

1982

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

The aim of the present investigation was to study the various regulatory mechanisms involved in the control of cAMP phosphodiesterases in rat skeletal myoblasts.;In rat skeletal myoblasts and adult muscle extracts, four forms of a high affinity cAMP phosphodiesterase are found in vitro. These are termed PDE I, PDE II, PDE III and PDE IV, and have approximately molecular weights of 1.5 x 10('6), 400,000, 120,000 and 60,000, respectively. Evidence is presented to show that there is only one primary form of phosphodiesterase in myoblasts, viz. PDE II, with the rest of the forms being derived from it.;In the presence of Bt(,2)cAMP or compounds which are able to augment in vivo concentrations of cAMP in the culture medium, the phosphodiesterase activity of skeletal myoblasts increases about 2-fold within 30 min of culture. Modification of PDE II can be demonstrated in cell-free extracts. Modification is entirely dependent on ATP and cAMP. Evidence is presented to show that during in vitro activation of phosphodiesterase, PDE II is phosphorylated.;When the myoblasts are exposed to Bt(,2)cAMP for 10-16 hours the activity of PDE III increases considerably. Spontaneous or Rous-Sarcoma virus-transformed myoblasts, however, show altered regulation of the two forms of PDE. In the presence of cAMP in the medium, unlike the nontransformed cells, the level of PDE III do not increase but the activity of PDE II rises. The altered moe of PDE regulation in transformed cells is dominant in hybrids between normal and transformed myoblasts.

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