IN-VIVO ISOPROTERENOL TREATMENT LEADS TO DOWN-REGULATION OF THE MESSENGER-RNA ENCODING THE CAMP RESPONSE ELEMENT-BINDING PROTEIN IN THE RAT-HEART

The expression of different myocardial regulatory proteins is altered in human heart failure, e.g., beta(1)-adrenoceptors, G-proteins and ot hers. Similar changes in rats after 4 days treatment with isoprotereno l led to the hypothesis of the cAMP pathway involved in these changes. In different cell types cAMP-dependent transcriptional activation is mediated by the cAMP-response element binding protein (CREB) which was recently shown to be expressed and phosphorylated in the human heart. Here, by the reverse transcriptase-polymerase chain reaction two alte rnatively spliced isoforms of CREB mRNA were found to be expressed in rat ventricles. Both isoforms were downregulated in the ventricles of rats treated in vivo with isoproterenol (2.4 mg/kg per day) for 4 days proposing a possible mechanism involved in expressional changes menti oned above. (C) 1995 Academic Press, Inc.