TYPE-V, BUT NOT TYPE-VI, ADENYLYL-CYCLASE MESSENGER-RNA ACCUMULATES IN THE RAT-HEART DURING ONTOGENIC DEVELOPMENT - CORRELATION WITH INCREASED GLOBAL ADENYLYL-CYCLASE ACTIVITY

Type V and VI adenylyl cyclase mRNAs are the two main cyclase isoforms expressed in the mammalian heart. A recent report has shown that thei r expression is differentially regulated during ontogenic development, but the accumulation of the two mRNA species and their concentration ratio have not been determined. We thus determined the accumulation an d the relative amounts of type V and VI adenylyl cyclase mRNA in fetal , neonatal and adult rat hearts, using a sensitive ribonuclease protec tion assay. In 18-day-old fetuses, the two adenylyl cyclase mRNA isofo rms were weakly expressed in approximately equal amounts (type V mRNA/ type VI mRNA = 0.93+/-0.09). Further development was characterized by a sharp increase in type V adenylyl cyclase mRNA (x 1.9 in neonates nu fetuses, P<0.01; x 2.4 and x 4.5 in adults nu neonates and fetuses, r espectively, P<0.01 for both comparisons) and a slight, non-significan t fall in type VI mRNA (P = 0.16). As a result, the type V mRNA/ type VI mRNA ratio was 2.86+/-0.57 and 9.09+/-1.21 in neonatal hearts and a dult ventricles, respectively (P<0.01 nu ratio in fetal hearts for bot h comparisons; P<0.01 for ratio in adult ventricles nu ratio in neonat al hearts), and the overall amount of the two mRNA isoforms was 2.3 ti mes greater in adult than in fetal hearts (P<0.01). This increase was paralleled by an increase in basal and isoproterenol- and forskolin-st imulated adenylyl cyclase activities in adult hearts compared to fetal and neonatal hearts (P<0.01 for the three comparisons). Our results d emonstrate that type V adenylyl cyclase mRNA accumulates in the rat he art after birth to become the highly predominant isoform in the adult heart. They further suggest that the increase in cardiac adenylyl cycl ase activity observed during rat development is due to this accumulati on. (C) 1995 Academic Press Limited