G proteins, adenylyl cyclase and related phosphoproteins in the developing rat heart.
The postnatal alterations of the composition of alpha subunit isoforms (Gi alpha c, Gi alpha 3, G(o) alpha, and Gq alpha) of G proteins, the adenylyl cyclase activity as well as of cAMP-regulated phosphoproteins e.g. troponin I and phospholamban were investigated in the ventricular tissue of 1, 7, 30 days old rats. Quantitative immunodetection revealed a 5.7-fold decrease in Gi alpha 3 at 30th postnatal day compared with the postnatal day 1 and up to 15-fold at 4 months. The amounts of Gq alpha and G(o) alpha as well as the G beta subunits were found to be higher in the earlier life period compared to the adult. In contrast, the content of Gs alpha was uneffected by the developmental state. Basal adenylyl cyclase activity (pmoles cAMP/min x mg protein) increased from 30.9 +/- 5.0, 36.8 +/- 5.0 to 63.9 +/- 5.9 at 1st, 7th and 30th postnatal day, respectively. Isoprenaline (100 microM) enhanced the activity of adenylyl cyclase from day 1, 7-30 from 46.2 +/- 7.0, 79.1 +/- 9.2 to 120.5 7.2, respectively. The effects of forskolin and NaF on adenylyl cyclase activity was found to be not influenced within the first postnatal month. Furthermore, a developmentally controlled expression of cardiac troponin I was observed (6-fold from the first to the 28th postnatal day) whereas the level of phospholamban was found to be age-independent. In conclusion, there is an increase in the efficiency of the beta-adrenergic signal transfer mainly caused by a reduction of the inhibitory G proteins and a dominance of the Gs alpha-linked pathway in the postnatal rat heart. Furthermore the developmentally controlled expression of troponin I might be of functional importance in the cAMP-supported relaxation. Additionally, altered Gq alpha, G(o) alpha and G beta pattern of the developing rat ventricle may play a role in the observed change of alpha-adrenerg-mediated heart contractility as well as in cardiac differentiation and growth processes.
Bartel
S
S
Max-Delbrück-Centrum für Molekulare Medizin, Forschungsschwerpunkt Kardiologie, Berlin, Germany.
Karczewski
P
P
Krause
E G
EG
D000262:Adenylyl Cyclases / Q000502:physiology*; D000375:Aging; D000818:Animals; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006321:Heart / Q000254:growth & development*; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology; D010750:Phosphoproteins / Q000502:physiology*; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D012969:Sodium Fluoride / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism
D010750:Phosphoproteins; D019210:Troponin I; D005576:Colforsin; D012969:Sodium Fluoride; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol