Phorbol esters and cyclic AMP activate AMP deaminase in adult rat cardiac myocytes

Bo Hu, Ruth A. Altschuld, Charlene M. Hohl*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Using rapid deenergization as a probe for adenylate deaminase activity in intact adult rat cardiac myocytes, we have previously established that IMP formation is enhanced by α-adrenergic agonists. In the present study, the effect of adrenergic agents on adenylate deaminase was further characterized. Phenylephrine (PE)3 increased IMP production in a dose-dependent fashion with an EC50 of 8 × 10-7 m. The response to PE was reversed within 10 min by the α1-antagonist, prazosin. Likewise, adenylate deaminase was also activated in ventricular myocytes challenged with phorbol 12-myristate 13-acetate (PMA, EC50 = 5 nm); cardiac cells presented with 100 nm PMA increased IMP production from 4.4 ± 0.5 (control) to 15.7 ± 0.9 nmol/mg protein when subsequently deenergized. The effects of PMA and PE were attenuated 85 ± 5% and 96 ± 4%, respectively, by pretreatment of cells with 150 nm staurosporine, an inhibitor of protein kinase C. Furthermore, incubation of cardiac cells with 1 μm PMA for 24 h blunted the response to both PMA and phenylephrine 85-90%. Elevating cyclic AMP (cAMP) content to >15 pmol/mg by treatment with forskolin or isoproterenol plus isobutylmethylxanthine also resulted in enhanced adenylate deaminase activity, but this stimulatory effect was not abolished by 24 h incubation with 5 μm PMA. Forskolin and PMA-induced increases in IMP production appeared to be additive. However, 0.5 μm isoproterenol inhibited the cellular response to phenylephrine by about 30% but did not affect PMA-stimulated adenylate deaminase activity. We conclude that both cAMP and protein kinase C stimulate adenylate deaminase, perhaps through selective activation of different isoforms. However, cAMP also exerts partial inhibition on α-adrenoreceptor-mediated increases in IMP production.

Original languageEnglish (US)
Pages (from-to)100-106
Number of pages7
JournalArchives of biochemistry and biophysics
Issue number1
StatePublished - Nov 15 1991

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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