Hormonally specific phosphorylation of cardiac troponin I and activation of glycogen phosphorylase

Abstract

WE recently reported that PGE₁ and isoprenaline have very different effects on the substrates of cyclic AMP-dependent protein kinase that regulate cardiac glycogen metabolism. Both agents elevated the cyclic" AMP content and the protein kinase activity ratio in isolated perfused rat hearts, but only isoprenaline caused changes in the activity of the substrates of protein kinase (presumably phosphorylation, causing activation of phosphorylase kinase and inactivation of glycogen synthase)^1,2. Thus, the activation of soluble protein kinase appears insufficient to a cause alteration of the regulatory enzymes of glycogen metabolism. This suggests that the gly-cogenolytic responses to isoprenaline involve actions other than the activation of soluble protein kinase. We now report the effects of PGE₁ and isoprenaline on another substrate of protein kinase, the inhibitory subunit of cardiac troponin (TNI). Since the phosphorylation of TNI may mediate the positive inotropic effects associated with β-adrenergic stimulation and cyclic AMP accumulation³, we felt that the hormonally specific expression of protein kinase activity might be used as a tool to determine whether similar specificity applies to the phosphorylation of TNI and to establish the functional relevance of that phosphorylation.