Immunolocalization of ornithine decarboxylase in rat heart atria.

Mammalian atrial myocytes secrete a potent natriuretic and diuretic factor, atrial natriuretic peptide (ANP), in response to volume expansion or elevations of right atrial pressure. ANP is synthesized in the atrial atrial myocytes and stored in cytoplasmic secretory granules. Ornithine decarboxylase (ODC) is the initial rate-limiting enzyme in the biosynthesis of polyamines, organic cations which are essential for various aspects of DNA, RNA and protein synthesis, structure, and function. The enzyme has been reported to be localized predominantly in the cytoplasm. A polyclonal antibody elicited against ODC was used to analyse the intracellular distribution of the enzyme protein within atrial myocytes at the ultrastructural level through the use of a post-embedding immunogold technique. In control animals, the density of gold particles associated with the atrial granules was seven to 30-fold higher than that detected in association with other subcellular structures. Administration of Isoproterenol increased atrial of Isoproterenol increased atrial ODC activity 18-fold and the density of the immunolabelling of the atrial myocytes five-fold. Statistically significant increases in the density of labelling after stimulation occurred in association with the atrial granules and the nucleus. After isoproterenol stimulation, 60% of the immunodetectable ODC protein in the atrial myocyte was found in association with the atrial granules. The atrial granules were demonstrated to contain ANP by immunocytochemical analysis of adjacent sections.

Isoprenaline induced changes in ornithine decarboxylase activity and polyamine content in regions of the rat heart.

Isoprenaline stimulated increases in ornithine decarboxylase activity and polyamine content in cardiac tissues are implicated in macromolecular synthesis and cellular growth, but little is known about polyamine metabolism in functionally distinct regions of the heart. We therefore determined regional changes in ornithine decarboxylase activity and polyamine content in the right and left ventricles, septum, and the right and left atria of the rat following the administration of isoprenaline. An increase in ornithine decarboxylase specific activity and tissue polyamine content occurred in all cardiac regions, but the highest ornithine decarboxylase activity was found in the septum. Propranolol inhibited the isoprenaline stimulated ornithine decarboxylase activity in all the regions. Putrescine increased and peaked between 6 and 8 h in right and left ventricles and septum and declined to a control level by 12 h. Following a peak increase at 8 h, spermidine and spermine contents of both ventricles were maintained at peak levels, while those in the septum declined to control values by 12 h. There was no detectable putrescine in the right atria from the control experiments and in either atrium at 2 h following isoprenaline administration. Putrescine content peaked at 6 h in the right atrium and at 8 h in the left atrium and then declined. In both atria there was a peak increase in spermidine and spermine contents between 4 and 8 h. These results show that there is a regional variation in the accumulation of polyamines in the rat heart following isoprenaline administration.

Regional changes in ornithine decarboxylase activity and polyamine levels during thyroxine-induced cardiac hypertrophy.

Ornithine decarboxylase activities (ODC) and polyamine levels were determined in five cardiac regions of the rat heart, following daily administration of 1 mg/kg of thyroxine, in the right and left atria, the right and left ventricles and the septum. The thyroxine stimulated ODC activity in all five regions of the heart. Enzyme activity in the left atrium and the septum peaked a day earlier than in other regions and the decline of ODC activity was slower. Putrescine in control animals was present in all regions except the right atrium, where its content was below detectable levels. Following the administration of thyroxine, the putrescine content of the left atrium, the right ventricle and the septum declined, while spermidine and spermine levels remained unchanged. In direct contrast to the other regions of the heart, thyroxine stimulated an increase in polyamines, as well as in weight which occurred exclusively in the left ventricle. These findings suggest a causal relationship between increased polyamines and hypertrophy.