Effect of thyroid status on phosphatidylinositols in rat heart.

Abstract

The incorporation of 32Pi into phosphatidylinositols and inositol trisphosphates was studied in Langendorff-perfused hearts from hypothyroid, euthyroid and hyperthyroid rats. The hearts were perfused with modified Krebs buffer containing [32P]orthophosphate and the degree of 32P-labeling of phosphatidylinositol, phosphatidylinositol 4-monophosphate, phosphatidylinositol 4,5-bisphosphate, inositol trisphosphates and phosphatidic acid was measured. Hyperthyroidism was associated with increases in rates of rise and fall of left ventricular systolic pressure, sarcoplasmic reticular Ca(2+)-ATPase activity and 32P-labeling of phosphatidylinositols, inositol trisphosphates and phosphatidic acid. These measurements were significantly decreased in hypothyroid hearts. The tissue levels of inositol 1,4,5-trisphosphate isoform were found to be significantly higher in hyperthyroid hearts and lower in hypothyroid hearts than in euthyroid ones. Examination of phosphoinositide-specific phospholipase C activity in the perfused hearts revealed that hyperthyroidism was associated with an increase in the membrane-associated enzymatic activity, assayed at physiological calcium concentrations, while hypothyroidism was associated with a decrease in this activity as compared with control hearts. These findings indicate that alterations in the thyroid state of the myocardium may be associated with changes in basal phosphoinositide turnover which may contribute to alterations in myocardial contraction.