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G proteins,adenylyl cyclase and related phosphoproteins in the developing rat heart
Authors:Bartel  Sabine  Karczewski  Peter  Krause  Ernst-Georg
Institution:(1) Max-Delbruck-Centrum fur Molekulare Medizin, Forschungsschwerpunkt Kardiologie, Robert-Rossle-Str 10, D-13125 Berlin, Germany
Abstract:The postnatal alterations of the composition of a subunit isoforms (Giagrc, G iagr3 Goagr, and Gqagr of G proteins, the adenylyl cyclase activity as well as of cAMP-regulated phosphoproteins e.g. troponin and phospholamban were investigated in the ventricular tissue of 1, 7, 30 days old rats. Quantitative immunodetection revealed a 5.7-fold decrease in Giagr3 at 30th postnatal day compared with the postnatal day 1 and up to 15-fold at 4 months. The amounts of Gqagr and Ginfin as well as the Gagr subunits were found to be higher in the earlier life period compared to the adult. In contrast, the content of Gsagr was uneffected by the developmental state. Basal adenylyl cyclase activity (pmoles cAMP/min × 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 mgrM) 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 inhibitiory G proteins and a dominance of the Gsagr-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 Gqagr, Goagr and Gbeta pattern of the developing rat ventricle may play a role in the observed change of agr-adrenerg-mediated heart contractility as well as in cardiac differentiation and growth processes.
Keywords:developing heart  G proteins  adenylyl cyclase  phosphoproteins
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