Biochemical changes in progressive muscular dystrophy. XII. Cyclic nucleotides in lymphoid and nonlymphoid organs of dystrophic mice

Abstract

Concentrations of cAMP and cGMP were measured (per milligram DNA) in the lymphoid (thymus, spleen) and nonlymphoid organs (liver, brain, kidney, lungs, heart, pancreas, skeletal muscle, lens) of normal (+/+) and dystrophic (dy/dy) 129 ReJ mice aged 30, 60, and 90 days. The cAMP concentrations in the thymus did not reveal any significant differences at 30 and 60 days of dystrophy, but were considerably higher (2-fold) at 90 days. cGMP concentrations were decreased in the thymus at 30 days (0.20-fold) and markedly elevated at 60 (2-fold) and 90 days (3-fold) of the disease. The [cAMP]/[cGMP] ratio was increased (1.30-fold) at 30 days of dystrophy, and this was followed by a sharp decline at 60 days (2-fold), with a lesser decrease at 90 days (0.34-fold). In the spleen, the cAMP concentrations were augmented significantly in all stages of dystrophy (1.5- to 2.6-fold). cGMP (per milligram DNA) did not show any significant variation at 30 and 60 days of the disease but was increased (3-fold) at 90 days. The [cAMP]/[cGMP] ratio, which was enhanced in the spleen at 30 (2-fold) and 60 days (1.5-fold), demonstrated no change at 90 days of dystrophy. These results indicated significant differences in the concentration of cyclic nucleotides and their ratios in the thymus and spleen of 129 ReJ dy/dy mice. The modifications were not limited to lymphoid organs alone, having been noted in the nonlymphoid organs as well. These changes could, in turn, influence immune responsiveness and could cause immunodepression in dystrophic mice.