G proteins-coupled signaling pathways appear to play a role in the development of cardiac hypertrophy and its progression to heart failure. The present study aimed to investigate trimeric G proteins and adenylyl cyclase signaling in immature as well as in adult rat myocardium during this process caused by pressure overload. Pressure overload was induced in newborn (2-day-old) rats by abdominal aortic banding and myocardial preparations from left ventricular myocardium of immature (10-day-old) and adult (90-day-old) animals were analyzed for the relative content of different G protein subunits and adenylyl cyclase (AC) by immunoblotting with specific antibodies. A functional status of the AC signaling system was also evaluated. Normal maturation of rat heart was accompanied by increased expression of AC type V/VI and VII and of the long isoform (G(s)alphaL) of G(s)alpha protein. In parallel, the amounts of myocardial G(i)alpha/G(o)alpha proteins tended to decrease, and G(q)alpha/G(11)alpha and Gbeta did not change. Interestingly, whereas fluoride-stimulated AC activity increased in the course of maturation, activity of AC measured under other experimental conditions (stimulation by Mn2+, forskolin or isoproterenol) was lower in adult than in young rat myocardium. Pressure overload did not influence distribution of G proteins in immature myocardium, but considerably decreased the content of G(s)alphaL and increased G(o)alpha proteins in hearts of 90-day-old rats. These hearts exhibited worsened functional reserve as compared to age-matched controls and activity of AC was also markedly lower. A considerable reduction in Mn(2+)-stimulated AC activity together with similar decrease in AC activity determined under other stimulation conditions suggests that it is a function of AC catalytic subunit that is primarily impaired in this model of pressure overload.

• MeSH
• Adenylyl Cyclases genetics   metabolism   MeSH
• Gene Expression MeSH
• Fluorides pharmacology   MeSH
• Hypertrophy, Left Ventricular metabolism   MeSH
• Isoproterenol pharmacology   MeSH
• Cardiomegaly genetics   metabolism   pathology   MeSH
• Cardiotonic Agents pharmacology   MeSH
• Colforsin pharmacology   MeSH
• Rats MeSH
• Manganese pharmacology   MeSH
• Myocardium metabolism   MeSH
• Animals, Newborn * MeSH
• Rats, Wistar MeSH
• Protein Isoforms genetics   metabolism   MeSH
• GTP-Binding Proteins metabolism   MeSH
• Signal Transduction MeSH
• Aging MeSH
• Pressure * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Adenylyl Cyclases MeSH
• Fluorides MeSH
• Isoproterenol MeSH
• Cardiotonic Agents MeSH
• Colforsin MeSH
• Manganese MeSH
• Protein Isoforms MeSH
• GTP-Binding Proteins MeSH

In vitro experiments suggest that stimulation of lipolysis by catecholamines in adipocytes depends on the energy status of these cells. We tested whether mitochondrial uncoupling proteins (UCPs) that control the efficiency of ATP production could affect lipolysis and noradrenaline signalling in white fat in vivo. The lipolytic effect of noradrenaline was lowered by ectopic UCP1 in white adipocytes of aP2-Ucp1 transgenic mice, overexpressing the UCP1 gene from the aP2 gene promoter, reflecting the magnitude of UCP1 expression, the impaired stimulation of cAMP levels by noradrenaline and the reduction of the ATP/ADP ratio in different fat depots. Thus only subcutaneous but not epididymal fat was affected. UCP1 also down-regulated the expression of hormone-sensitive lipase and lowered its activity, and altered the expression of trimeric G-proteins in adipocytes. The adipose tissue content of the stimulatory G-protein alpha subunit was increased while that of the inhibitory G-protein alpha subunits decreased in response to UCP1 expression. Our results support the idea that the energy status of cells, and the ATP/ADP ratio in particular, modulates the lipolytic effects of noradrenaline in adipose tissue in vivo. They also demonstrate changes at the G-protein level that tend to overcome the reduction of lipolysis when ATP level in adipocytes is low. Therefore, respiratory uncoupling may exert a broad effect on hormonal signalling in adipocytes.

• MeSH
• Adenosine Diphosphate metabolism   MeSH
• Adenosine Triphosphate metabolism   MeSH
• Cyclic AMP metabolism   MeSH
• DNA Primers MeSH
• Genotype MeSH
• Hepatocytes enzymology   MeSH
• Ion Channels MeSH
• Lipase genetics   MeSH
• Lipolysis * MeSH
• Membrane Proteins genetics   physiology   MeSH
• Mitochondrial Proteins MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Norepinephrine metabolism   MeSH
• GTP-Binding Proteins metabolism   MeSH
• Gene Expression Regulation, Enzymologic MeSH
• Base Sequence MeSH
• Carrier Proteins genetics   physiology   MeSH
• Adipose Tissue enzymology   metabolism   MeSH
• Uncoupling Protein 1 MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenosine Diphosphate MeSH
• Adenosine Triphosphate MeSH
• Cyclic AMP MeSH
• DNA Primers MeSH
• Ion Channels MeSH
• Lipase MeSH
• Membrane Proteins MeSH
• Mitochondrial Proteins MeSH
• Norepinephrine MeSH
• GTP-Binding Proteins MeSH
• Carrier Proteins MeSH
• Ucp1 protein, mouse MeSH Browser
• Uncoupling Protein 1 MeSH