Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type V and VI adenylyl cyclase mRNAs are the two main cyclase isoforms expressed in the mammalian heart. A recent report has shown that their 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 and the relative amounts of type V and VI adenylyl cyclase mRNA in fetal, neonatal and adult rat hearts, using a sensitive ribonuclease protection assay. In 18-day-old fetuses, the two adenylyl cyclase mRNA isoforms 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 v fetuses, P < 0.01; x 2.4 and x 4.5 in adults v neonates and fetuses, respectively, P < 0.01 for both comparisons) and a slight, non-significant 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 adult ventricles, respectively (P < 0.01 v ratio in fetal hearts for both comparisons; P < 0.01 for ratio in adult ventricles v ratio in neonatal hearts), and the overall amount of the two mRNA isoforms was 2.3 times greater in adult than in fetal hearts (P < 0.01). This increase was paralleled by an increase in basal and isoproterenol- and forskolin-stimulated adenylyl cyclase activities in adult hearts compared to fetal and neonatal hearts (P < 0.01 for the three comparisons). Our results demonstrate that type V adenylyl cyclase mRNA accumulates in the rat heart after birth to become the highly predominant isoform in the adult heart. They further suggest that the increase in cardiac adenylyl cyclase activity observed during rat development is due to this accumulation.
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PMID:Type V, but not type VI, adenylyl cyclase mRNA accumulates in the rat heart during ontogenic development. Correlation with increased global adenylyl cyclase activity. 852 40

Granulosa cells are essential for follicular development and corpus luteum formation and their functions are regulated by gonadotrophins through G protein-coupled receptors. The dominant second messenger pathway involves the stimulation of cyclic AMP formation by G alpha s-linked receptors. In this paper we have investigated the expression of G alpha s mRNA splice variants in relation to expression of G alpha s protein isoforms in granulosa cells obtained from patients undergoing in vitro fertilization. We have carried out ribonuclease protection assays using cRNA riboprobes which are capable of detecting all G alpha s mRNA isoforms as well as quantifying total amounts of G alpha s mRNA. Granulosa cells express the message for G alpha s-Large and G alpha s-Small and the presence of two distinct protein products was confirmed by immunoblotting using the antibody RM/1. Moreover, the data show that a significant fraction of G alpha s-Large and G alpha s-Small mRNAs contain an extra CAG codon. This should generate proteins with an extra serine residue, resulting in G alpha s variants with the consensus sequence of a protein kinase C phosphorylation site. These results highlight the possible interaction between different signalling pathways in the control of cAMP production and the need to investigate the relationship between G alpha s variants and different adenylyl cyclase isozymes in patients with normal and abnormal ovarian function.
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PMID:Identification of G alpha s messenger ribonucleic acid splice variants in human granulosa cells. 906 4

We determined the effect of long-term exposure to beta-agonists on beta(1)-adrenergic receptors (beta(1)-AR) in human neuroepithelioma SK-N-MC cells because earlier studies have indicated that beta(1)-AR in this cell line are resistant to agonist-induced down-regulation. Exposing SK-N-MC cells to isoproterenol for 24 hr reduced the density of beta(1)-AR by 72%, whereas forskolin, an activator of all the isoforms of adenylyl cyclase, failed to affect the density of beta(1)-AR. Measurement of beta(1)-AR mRNA levels by the ribonuclease protection assay revealed that isoproterenol-induced down-regulation of beta(1)-AR was associated with a sharp decline in beta(1)-AR mRNA, while forskolin also failed to affect this parameter. The differences between the effects of isoproterenol and forskolin on beta(1)-AR were unrelated to cyclic AMP levels, since both agents increased cyclic AMP equally. Next, we determined the role of cyclic AMP-dependent protein kinase A (PKA) in this phenomenon. Inhibition of PKA by its specific inhibitor, H-89 [N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, 2HCl], markedly reduced the magnitude of the isoproterenol-mediated down-regulation of the beta(1)-AR and its mRNA. Transient expression of the catalytic subunit of PKA in SK-N-MC cells down-regulated beta(1)-AR independently of isoproterenol. Therefore, PKA is central to the effect of beta-agonists in down-regulating beta(1)-AR, and its spatial compartmentalization and access to the receptor appear to be essential components of its action.
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PMID:Regulation of human beta(1)-adrenergic receptors and their mRNA in neuroepithelioma SK-N-MC cells: effects of agonist, forskolin, and protein kinase A. 1170 54