EFFECT OF PROTEIN-KINASE-C ON CYCLIC 3',5'-ADENOSINE MONOPHOSPHATE-DEPENDENT PHOSPHODIESTERASE IN HYPERTROPHIC CARDIOMYOPATHIC HAMSTER HEARTS

''Cross-talk,'' or interaction between different signal transduction p athways, is known to exist in noncardiac cells, but it has not been de monstrated previously in mammalian hearts. We found that hypertrophic cardiomyopathic Syrian hamster (BIG 14.6, 6 months old) hearts were de ficient in cyclic 3',5'-adenosine monophosphate (cAMP) [11.9 +/- 0.4 v s. 15.4 +/- 0.4 pmol/mg protein in age-matched control hamsters (BIG R B), n = 6, P =.0005] but not in cyclic 3',5'-guanosine monophosphate ( 1.23 +/- 0.10 vs. 1.34 +/- 0.18 pmol/mg protein in BIO RB, n = 6, P = N.S.). The reduction in cAMP was at least partly accounted for by an i ncrease in the cytosolic phosphodiesterase (PDE) activity in BIO 14.6 hearts (1709 +/- 119 vs. 1341 +/- 113 pmol/min/mg protein in age-match ed BIO RBs, n = 12, P = .006), suggesting that there is an increase in cAMP turnover in BIO 14.6 hearts. Protein kinase C (PKC) activities w ere also significantly elevated in BIO 14.6 hearts (77.9 +/- 2.1 vs. 5 4.6 +/- 3.3 pmol/min/mg protein in BIO RBs, n = 6, P < .001). Activati on of PKC by phorbol 12-myristate 13-acetate (PMA, 10 mu M) produced s ignificant potentiation in PDE activities in BIO 14.6 but not in BIO R B hearts, and the PMA-induced increase in PDE activity could be blocke d by the PKC-specific pseudosubstrate inhibitor peptide PKC(19-31). Re moval of PKC by incubation with PKC-specific antibodies and then with protein A-agarose eliminated the ability of PMA to stimulate PDE in BI O 14.6 hearts, suggesting that activation of PKC produced potentiation of PDE activity in hypertrophic BIO 14.6 hearts and may lead to accel eration in degradation of cAMP. Activation of PKC by PMA resulted in a 2-fold increase in the V-max value without changing the K-M value of PDE in BIO 14.6 hearts, and such effects were not present in BIO RB he arts. These results indicate that there is ''cross-talk'' between PKC and the cAMP regulatory pathways in BIO 14.6 hearts but not in BIO RE hearts. Such ''cross-talk'' may cause acceleration in cAMP degradation , resulting in cAMP deficiency and its associated abnormalities in exc itation-contraction coupling in BIO 14.6 hearts.