Linked Life Data

8227073

Source:http://linkedlifedata.com/resource/pubmed/id/8227073

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
1993-12-20
pubmed:abstractText
Angiotensin II stimulates the hepatic synthesis and secretion of angiotensinogen, the substrate of renin. In the present study performed on freshly isolated rat hepatocytes we demonstrate that this effect of angiotensin II is mainly related to a transient inhibition of adenylylcyclase. Agents known to decrease intracellular cAMP (angiotensin II, vasopressin, guanfacine) or the cAMP-antagonist Rp-adenosine-3',5'-cyclic phosphothioate stimulated, whereas cAMP-stimulating agents (isoproterenol, forskolin, glucagon) or the cAMP-agonist Sp-adenosine-3',5'-cyclic phosphothioate inhibited angiotensinogen synthesis. In contrast, all agents known to affect intracellular concentrations of calcium, as confirmed in Fura-2-loaded hepatocytes (Bay K 8644, calcimycin, calmidazolium, ionomycin, or methoxamine) failed to influence the synthesis of angiotensinogen. The inhibitory effect of angiotensin II as well as the stimulatory effect of glucagon on cAMP were inversely related to angiotensinogen mRNA and angiotensinogen secretion over a wide concentration range of both peptides. Both the angiotensin II-dependent inhibition of cAMP and the angiotensin II-induced increase in angiotensinogen mRNA were abolished by a pertussis toxin pretreatment. In hepatocyte membranes, pertussis toxin ADP-ribosylated a single protein (approximately 41 kDa) probably representing the alpha-subunit of the Gi-protein, coupling inhibitory receptors to adenylylcyclase. We further show that the increase of angiotensinogen mRNA and secretion mainly represents the result of mRNA stabilization, since in a nuclear run-on assay, angiotensin II pretreatment of hepatocytes does not significantly alter the rate of [32P]UTP incorporation into angiotensinogen mRNA, whereas angiotensin II prolonged the half-life of angiotensinogen mRNA in transcription-arrested as well as in [3H]uridine pulse-labeled hepatocytes about 2.5-fold from 80 to 190 min. It is concluded that angiotensin II induces an increase in angiotensinogen synthesis in hepatocytes by stabilizing of angiotensinogen mRNA and that this effect is mediated through inhibition of adenylylcyclase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25095-107
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Angiotensin II stimulates the synthesis of angiotensinogen in hepatocytes by inhibiting adenylylcyclase activity and stabilizing angiotensinogen mRNA.
pubmed:affiliation
Department of Pharmacology, University of Heidelberg, Federal Republic of Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't