[Beta adrenergic signal transduction and heart adenyl cyclase].
Transduction of the beta-adrenergic signal plays an important role in the regulation of cardiac contractility. It is mediated by three sarcolemmal proteins: the beta-adrenergic receptor, G proteins and adenylyl cyclase which is the catalytic unit of the system which generates cAMP, the second messenger of the system. Each protein comprises a number of isoforms which yields a wide range of potential regulations, many of which are not yet elucidated. Among the three proteins, the adenylyl cyclase is the one which has been less studied. However, the recent cloning of many of its isoforms allows now investigations of their expression in many tissues and cell types. We have shown in rats that among the five isoforms detected in the myocardium, type V and VI adenylyl cyclase mRNAs are the most abundant ones. Type V and VI adenylyl cyclase mRNA abundance is similar in late fetal hearts. Type V mRNA accumulates in the heart during postnatal development whereas type VI mRNA concentration remains unchanged. Consequently, type V mRNA becomes highly predominant compared to type VI mRNA in the adult rat ventricle (type V/type VI adenylyl cyclase mRNAs approximately 10). Whatever the developmental stage, cardiac adenylyl cyclase activity is inhibited by submicromolar calcium concentrations. In adult ventricles, adenylyl cyclase activity in the presence of 1 mM ATP is at least three times higher than that observed in fetal and new born rat hearts. Since this increase parallels the accumulation of type V adenylyl cyclase mRNA, one can hypothesize that the former is due to the latter. In contrast, our preliminary results seem to indicate that during heart failure in rats, decreased adenylyl cyclase activity is not associated with decreased cardiac concentrations of type V and VI adenylyl cyclase mRNAs. Isoform specific antibodies are now required to understand the reasons for such discrepancy.
Mercadier
J J
JJ
Laboratoire de Cardiologie Moléculaire et Cellulaire, CNRS URA 1159, Hôpital Marie-Lannelongue, Le Plessis Robinson, France.
Espinasse
I
I
Iourgenko
V
V
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006321:Heart / Q000254:growth & development; D006331:Heart Diseases / Q000378:metabolism; D006803:Human Development; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases