Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conservation of amino acid sequence among types I-IV adenylylcyclase has made it possible to apply the polymerase chain reaction to examine the extent of the molecular diversity within this family of enzymes. cDNA templates from rat heart, liver, kidney, guinea pig brain and testes, and mouse skeletal muscle were amplified with primers specific to adenylylcyclase sequences. Evidence was obtained for a total of eight distinct gene products divisible into five subfamilies. Five of the products correspond to regions from cloned forms of adenylylcyclase, while three are previously unidentified. As many as seven different adenylylcyclases are expressed in rat heart, liver, and kidney based on this analysis. Two newly identified polymerase chain reaction (PCR) products were utilized to screen a rat cDNA library from H35 Reuber hepatoma cells. A 6080-nucleotide cDNA contains an open reading frame encoding the 1166-amino acid type VI protein which has a predicted topography similar to that of other adenylylcyclases. The type VI message is abundantly expressed in rat heart, kidney, and brain. Human embryonal kidney cells stably expressing the cDNA showed an enhanced response to isoproterenol that could be inhibited by carbachol in intact cells. Increases in intracellular Ca2+ contribute to the inhibitory effect of carbachol.
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PMID:Molecular diversity in the adenylylcyclase family. Evidence for eight forms of the enzyme and cloning of type VI. 133 69

Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.
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PMID:[The adrenergic beta system in an experimental model of heart failure]. 196 56