EFFECT OF THYROID STATUS ON PHOSPHATIDYLINOSITOLS IN RAT-HEART

The incorporation of (32)Pi into phosphatidylinositols and inositol tr isphosphates was studied in Langendorff-perfused hearts from hypothyro id, euthyroid and hyperthyroid rats. The hearts were perfused with mod ified Krebs buffer containing [P-32]orthophosphate and the degree of P -32-labeling of phosphatidylinositol, phosphatidylinositol 4-monophosp hate, phosphatidylinositol 4,5-bisphosphate, inositol trisphosphates a nd phosphatidic acid was measured. Hyperthyroidism was associated with increases in rates of rise and fall of left ventricular systolic pres sure, sarcoplasmic reticular Ca2+-ATPase activity and 32-P-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 hypoth yroid hearts than in euthyroid ones. Examination of phosphoinositide-s pecific phospholipase C activity in the perfused hearts revealed that hyperthyroidism was associated with an increase in the membrane-associ ated enzymatic activity, assayed at physiological calcium concentratio ns, while hypothyroidism was associated with a decrease in this activi ty as compared with control hearts. These findings indicate that alter ations in the thyroid state of the myocardium may be associated with c hanges in basal phosphoinositide turnover which may contribute to alte rations in myocardial contraction.